69 results about "Cisplatin resistance" patented technology

The invention discloses a tetravalent platinum complex with a bioactive group and a preparation method of the tetravalent platinum complex. The tetravalent platinum complex is a platinum (IV) complex and has the structure shown in the formula II (please see the formula in the description), wherein in the formula II, Y is OH or Cl, and Bio represents the bioactive group. The platinum (IV) complex is prepared according to the equation in the formula III (please see the formula in the description), wherein in the formula III, Y is OH or Cl, Bio-OH represents a compound with bioactivity, TBTU represents a coupling agent O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, TEA represents a catalyst triethylamine, DMF represents solvent N,N-dimethyl formamide, and DMSO represents solvent dimethylsulfoxide. Cis-platinum is adopted for the bottom face of an octahedron, a small-molecular targeted or medicine active group is introduced to one axial position, a hydroxyl group or helium atom is introduced into another axial position, and the anti-tumor tetravalent platinum complex overcoming cisplatin resistance is provided, so the high-efficiency and low-toxin platinum (IV) complex is obtained.

The invention provides methods for predicting whether an ovarian cancer patient's tumor will be resistant to chemotherapy. The invention also provides methods for monitoring the effectiveness of treatment, particularly a chemotherapeutic treatment, in a patient treated for ovarian cancer. The invention further provides methods for treating ovarian cancer, by reducing chemotherapeutic drug resistance in said cells. In addition, the invention provides methods of screening compounds to identify tumor cell growth inhibitors in tumor cells resistant to conventional chemotherapeutic treatment regimes.

The invention provides a compound having anticancer activity, which is obtained by cooperation of Norabieta cantharidin and platinum (IV) and modification of a piperazine derivative. The compound is characterized in that a Norabieta cantharidin piperazine derivative ligand is introduced, thereby cytotoxicity of a platinum (IV) compound is reduced, and high antineoplastic activity is provided. The result of the cytotoxicity experiments shows that the provided platinum (IV) compound has less destruction to normal mice fibroblast L929, but has good killing effect to cancer cells such as human breast cancer MCF-7 cell, human cervical carcinoma HeLa cell and human lung adenocarcinoma A549 cell, so that the compound having anticancer activity is capable of reducing the system toxicity and having equal anticancer activity with cisplatin. The compound having anticancer activity has good killing effect by aiming at cisplatin resistance human lung adenocarcinoma A549 / DDP cell. Therefore, the toxicity is reduced, the cisplatin resistance can be reversed, and anticancer effect of the platinum medicines can be increased.

The invention discloses application of an iridium complex in preparing mitochondria targeted anti-tumor drugs. The structural formula of the iridium complex is [Ir(ppy)2(HPIP)]C1, wherein ligand represented by ppy is 2-phenylpyridine, ligand represented by HPIP is 3-(1H-imidazole[4,5-f][1,10]phenanthroline-2-yl)phenol. The iridium complex has the high inhibiting effect on human tumor cells HeLa, HepG2, A-549 and a cisplatin resistant strain CP / R-A549, mitochondria in tumor cells can be stored up, tumor cell apoptosiss can be induced, and the iridium complex can serve as the new anti-tumor drugtaking tumor cell mitochondria as target sites.

The invention provides an anti-tumor tetravalent platinum complex with an anti-drug resistance function and a preparation method thereof. The structural formula of the compound is shown as a formula Ior a formula II, and the compound is one of the following structures: the compound has excellent cytotoxic activity to tumor cells, especially to cisplatin-resistant tumor cells, and shows excellenttumor inhibition effect and relatively low toxicity in vivo.

The disclosure relates to a method for culture of a cis-platinum drug-resistant lung cancer organoid. The method comprises the following steps: mixing cis-platinum drug-resistant lung cancer tissue cells with the medium and matrix gel to obtain a to-be-cultured substance, wherein the medium contains matrix metalloproteinase-10, and the concentration of the matrix metalloproteinase-10 is 50-200nM based on the medium; and carrying out culture amplification on the to-be-cultured substance to obtain the cis-platinum drug-resistant lung cancer organoid. According to the culture method for the cis-platinum drug-resistant lung cancer organoid provided by the invention, since the employed medium contains the matrix metalloproteinase-10 with specific concentration, and the matrix metalloproteinase-10 with the specific concentration can promote in-vitro growth of the cis-platinum drug-resistant lung cancer organoid, the success rate of the culture is high when the method provided by the disclosure is used for the culture of the cis-platinum drug-resistant lung cancer organoid.

Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and / or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.

The invention discloses an application of ruthenium complex in antitumor drug preparation. The ruthenium complex is a delta configuration in a chiral molecule, and the structure formula is delta-[Ru(bpy)2(HPIP)](C1O4)2, wherein, HPIP is 2-(2-hydroxyphenyl) imidazole [4, 5-f] [1,10] phenanthroline. The ruthenium complex has strong inhibition effects for human tumor cells HeLa, A-549, BEL-7402, HepG2, MCF-7 and DDP-resistant line CP / R-A549, and has little toxicity for human normal hepatocyte LO2, and can induce the tumor cells to generate apoptosis by mitochondria apoptosis pathway. According to in vivo experiment of animals, ruthenium complex can substantially inhibit growth of subcutaneous human derived transplantation tumor of nude mouse, and under the treatment dosage, no toxicity relative to the complex is detected, thereby the product can be applied to preparation of novel antineoplastic active medicament whose target is mitochondria.

The invention discloses a PDZ protein molecule NHERF1 related to cisplatin resistance, and applications thereof, and belongs to the field of biological treatment of tumors. The invention further discloses a PDZ protein molecule NHERF1 related to cisplatin resistance, wherein the PDZ protein molecule NHERF1 is lowly expressed in cisplatin-resistant cervical cancer cell lines and is the new cisplatin-resistant cervical cancer marker, such that the new target is provided for the design of drugs resisting the cisplatin resistance of cervical cancers, and the new drug directly for the cisplatin resistance of cervical cancers can be designed and developed based on the new target; and the PDZ protein molecule NHERF1 has the biological function and mechanism of the promotion of the drug resistanceof cervical cancer cells so as to provide the effective approach for the effective reversing of the cisplatin resistance of cervical cancers and the improving of the clinical chemotherapy effects ofcervical cancers.

The present disclosure belongs to the field of anti-ovarian cancer drugs, and specifically relates to an application of PDZ-binding kinase as an ovarian cancer cisplatin-resistant target. The relationship between PDZ kinase and ovarian cancer as well as between PDZ kinase and a cisplatin-resistance mechanism in the prior art is not studied. In order to clarify the mechanism of cisplatin resistancein patients with ovarian cancer, the invention provide better treatment for patients with ovarian cancer. By aiming at the expression content of PBK and cisplatin-resistance condition of patients with ovarian cancer, the research shows that the high expression of PBK is positively correlated with the poor prognosis of the patients with ovarian cancer, further studies indicate that PBK overexpression promotes autophagy in ovarian cancer cells, and the ovarian cancer cell resistance to cisplatin is induced by promoting autophagy. The application uses a PBK inhibitor in combination with cisplatin for the treatment of ovarian cancer, and the therapeutic effect is superior to that of cisplatin alone.

The invention discloses application of long-chain non-coding RNA and an inhibitor of the long-chain non-coding RNA in prevention and treatment of breast cancer, a full-length sequence of the long-chain non-coding RNA LINC01778V2 is cloned for the first time, and the long-chain non-coding RNA LINC01778V2 is differentially expressed in cis-platinum drug-resistant breast cancer and cis-platinum sensitive breast cancer. Therefore, by detecting the LINC01778V2, the diagnosis of the cis-platinum drug resistance of the breast cancer can be realized. Meanwhile, the LINC01778V2 corresponding expression inhibitor can inhibit proliferation of breast cancer tumor cells, promote apoptosis of the breast cancer tumor cells, kill the tumor cells and reverse cisplatin resistance of cisplatin-resistant triple negative breast cancer. The invention also discloses application of the corresponding inhibitor in prevention and treatment of the triple negative breast cancer with cis-platinum resistance.

The invention discloses application of RBMS3 as a molecular target for tumor drug resistance detection, treatment and prognosis. Inventors find that RBMS3 deletion can promote tumor cisplatin-resistance and tumor recurrence. In the prior art, most tumor therapeutic schedules are surgical resection with adjuvant chemotherapy, and chemotherapy resistance becomes an important factor affecting the prognosis of tumor patients. A specific molecular marker is disclosed and can be used as an important molecular marker for predicting tumor drug resistance. The target gene can be detected at DNA level,and DNA is stronger in stability than RNA or proteins, and can improve the accuracy and limitation of diagnosis. A targeted therapeutic schedule is provided for the treatment of the tumor patients. Abetter therapeutic effect on patients with no RBMS3 deletion tumors can be obtained by use of cisplatin alone; and a better therapeutic effect on patients with RBMS3 deletion tumors can be obtained bycombined use of cisplatin and PRI-724.

The invention discloses a human gastric cancer cell line with 5-fluorouracil resistance and an establishing method and application thereof. The human gastric cancer cell line is preserved in China Center for Type Culture Collection and has a preservation number of CCTCC NO:2013154. The human gastric cancer cell line has the advantages of stable characters, stable multiple passages, high tumor formation rate, short incubation period and good uniformity, and provides a novel experimental material closer to the biological characteristics of clinical tumor for the study of gastric carcinoma. The human gastric cancer cell line has tumorigenicity; the generated tumor has 5-fluorouracil resistance and can be used to analyze the in vitro and in vivo drug sensitivity and resistance correlation, and then establish in vitro and in vivo two related drug screening platforms; and the is cell line is ideal for basic research of gastric cancer and clinical early stage application.

The invention discloses an indium complex taking APT as a ligand and having a potential leaving group as well as a synthesis method and application of the indium complex. The synthesis method comprises the following steps: dissolving 2-acetylpyridine in a mixed solution of methanol and acetonitrile, adding aminothiourea, uniformly mixing the mixture, dropwise adding acetic acid, uniformly mixing the mixture, refluxing the mixed solution, performing vacuum concentration to obtain a concentrate, extracting the concentrate with ethyl acetate, washing a product with saturated sodium bicarbonate and water in order after the extraction step, and carrying out silica gel column chromatography separation to obtain a ligand; adding the ligand obtained in the step 1) and INCl3 into a closed reactionkettle, dropwise adding a mixed solution of methanol and ethanol for dissolving, sealing the reaction kettle after dissolving, and standing the reaction kettle in a vacuum drying oven at 65-80 DEG C for 72 hours to obtain the indium complex. The complex shows good inhibition activity on a cisplatin drug-resistant strain, new data is provided for application of the novel metal-based complex to drug-resistant tumor cell strains, and the synthesis method is simple to operate and convenient to implement.

The invention discloses a tetravalent platinum complex containing artesunate. The structure of the tetravalent platinum complex is shown as a general formula I or II, wherein R is shown in the specification, and R1 is a branched chain or straight chain saturated C1-C20 alkyl group, or a branched chain or straight chain unsaturated C1-C20 alkyl group. The tetravalent platinum complex containing artesunate provided by the invention has an obvious proliferation inhibition effect on liver cancer HepG2, lung cancer A549, intestinal cancer HCT116, breast cancer MDA-MB-231 and cis-platinum drug-resistant lung cancer, the anti-tumor activity of part of compounds is obviously superior to that of cis-platinum, and the tetravalent platinum complex containing artesunate can be used as anti-tumor candidate drugs for deeper research.

The invention discloses three ursolic acid piperazine dithioformic acid-pyridine ruthenium complexes as well as a preparation method and application thereof. The preparation method of the ursolic acidpiperazine dithioformic acid-pyridine ruthenium complexes comprises the steps: respectively putting ligand ursolic acid piperazine dithioformic acid sodium and tris(2,2'-dipyridyl)ruthenium dichloride, tris(1,10-phenanthroline)ruthenium dichloride or tris(4,7-diphenyl-1,10-phenanthroline)ruthenium dichloride into a first organic solvent for coordination reaction, and thus obtaining a corresponding target crude product. Tests of the applicant show that the complexes have extremely remarkable inhibitory activity on certain tumor cell strains, the inhibitory activity is greatly higher than thatof parent nucleus and cis-platinum of the complexes, meanwhile, the inhibitory activity of the complexes on cis-platinum drug-resistant strain cells is remarkably superior to that of cis-platinum, andthe complexes are expected to be used for preparing anti-tumor drugs.

Disclosed is a cisplatin-resistance marker for determining whether ovarian tumor cells of interest are resistant to cisplatin.The cisplatin-resistance marker of the present invention includes a polynucleotide having any one of the base sequences of SEQ ID NOs. 1 to 11 and can be used in a detection method involving the following steps (1) to (3) to determine whether ovarian tumor cells of interest are resistant to cisplatin:(1) hybridizing RNA prepared from a biological sample from a subject, or a complementary polynucleotide transcribed from the RNA, with the cisplatin-resistance marker;(2) quantifying the RNA from the biological sample, or the complementary polynucleotide transcribed from the RNA, that has hybridized with the cisplatin-resistance marker, using the cisplatin-resistance marker as an index; and(3) determining whether the biological sample is a cisplatin-resistant ovarian tumor based on the results of the quantification.

The invention belongs to the field of anti-cervical cancer drugs, and particularly relates to application of T-LAK cell-originated protein kinase (TOPK) serving as a cisplatin resistance therapy target for cervical cancer. In the prior art, a relationship between the TOPK and cervical cancer proliferation and cisplatin resistance is not yet studied. In order to clarify the mechanism of cisplatin resistance of cervical cancer patients, and provide a better therapeutic drug for the cervical cancer patients, the invention conducts a series of researches on the influences of TOPK on cervical cancer proliferation and cisplatin resistance. Results show that the TOPK is highly expressed in tissue of the cervical cancer patients, the TOPK promotes proliferation of cervical cancer cells, and overexpression of the TOPK promotes cisplatin resistance of the cervical cancer cells. A further study shows that a TOPK specific inhibitor OTS514 significantly inhibits proliferation of the cervical cancercells in vivo and in vitro, and the TOPK inhibitor OTS514 and cisplatin are combined and applied to therapy of the cervical cancer, and the therapy effect is superior to a pure cisplatin cisplatin therapy effect.

The invention discloses a human gastric cancer cell line with cisplatin resistance and an establishing method and application thereof. The human gastric cancer cell line is preserved in China Center for Type Culture Collection, and has a preservation number of CCTCC NO:C2013152. The human gastric cancer cell line has the advantages of stable characters, stable multiple passages, high tumor formation rate, short incubation period and good uniformity, and provides a novel experimental material closer to the biological characteristics of clinical tumor for the study of gastric carcinoma. The human gastric cancer cell line has tumorigenicity, and the generated tumor has cisplatin resistance; compared with the passage parental tumor, the generated tumor can be used to analyze the in vitro and in vivo drug sensitivity and resistance correlation, and then establish in vitro and in vivo two related drug screening platforms; and the is cell line is ideal for basic research of gastric cancer and clinical early stage application.

The invention discloses miR-517a-3p related to cisplatin resistance of tumor cells and an application of the miR-517a-3p. The invention also discloses a kit for detecting the drug resistance degree oftumor cells to cisplatin. According to the miR-517a-3p, by establishing an SK-OV-3 / DDP drug-resistant cell strain, it is found that miR-517a-3p can be used as a marker of drug resistance of tumor cells; the miR-517a-3p plays a certain role in the drug resistance of the SK-OV-3 / DDP cells to the DDP, and the drug resistance of the SK-OV-3 / DDP cells to the DDP can be reversed by down-regulating themiR-517a-3p; in addition, the proliferation speed of ovarian cancer SK-OV-3 / DDP cells can be inhibited, and meanwhile, the cloning formation capability of the ovarian cancer SK-OV-3 / DDP cells is alsoinhibited. The miR-517a-3p is advantaged in that a scientific basis is provided for searching a new molecular treatment target, guiding clinical medication and more effectively resisting cisplatin resistance.

The invention discloses a tetravalent platinum complex with functions of targeted inhibition of AKR1C3 and reversal of tumor drug resistance and a preparation method thereof. The preparation method is simple in process, convenient to operate, safe to operate and good in product stability. The prepared target tetravalent platinum complex shows a relatively strong AKR1C3 inhibition effect on a cellular level, shows relatively good proliferation inhibition activity on tumor cells without drug resistance and cisplatin-resistant tumor cells, and can promote apoptosis of the tumor cells by inducing autophagy, so that a relatively good tumor treatment effect is achieved. The target tetravalent platinum complex is clear in targeting and small in toxic and side effects, and can be used as a novel anti-tumor drug to cope with increasingly severe anti-cancer situations.

The invention provides an anti-tumor compound capable of overcoming cis-platinum drug resistance and preparation and application thereof, the anti-tumor compound capable of overcoming cis-platinum drug resistance has a structure as shown in a compound 1 and a compound 2 as shown in a formula I. In view of serious toxicity and drug resistance of cis-platinum in clinical application, the invention aims to solve the technical problem that a novel platinum (II) compound is designed and synthesized by combining a compound with a known platinum (II) compound containing a functional group according to the characteristic that the compound with the activity of inhibiting protein kinase 2 can inhibit DNA (Deoxyribonucleic Acid) damage repair, and the obtained compound has a very strong inhibition effect on cisplatin-sensitive tumors and cisplatin-resistant tumors, is relatively low in toxicity, has the characteristics of high efficiency and low toxicity, and can be used for preparing anti-tumor drugs.

The invention discloses an application of a class of alkaloids in reversing cisplatin resistance of lung cancer. Cisplatin (DDP) is the first-line chemotherapy drug after lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compounds TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, and TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, in which TC-1, and TD-1 not onlycan reverse drug resistance, but also enhance the sensitivity of lung cancer cells to cisplatin. A compound TB-4 does not have this effect.

The invention discloses a synthesis method and application of a binuclear zinc complex, which comprises the following steps: synthesizing a Schiff base ligand by using o-vanillin and 4, 4-dimethyl-3-thiosemicarbazide as raw materials, and reacting the ligand with zinc chloride to obtain the zinc complex. The synthesized zinc complex has good inhibitory activity on a human lung cancer cell strain A549, has good inhibitory activity on a human lung cancer cell cis-platinum drug-resistant strain A549cisR, and is suitable for preparing efficient antitumor drugs.

The invention belongs to the field of medicinal chemistry, and in particular relates to a cisplatin-derived tetravalent platinum anticancer complex containing ursolic acid ligands and a preparation method and application thereof. The series of Pt(IV) complexes containing ursolic acid ligands disclosed by the present invention take cisplatin as the basic core, introduce ursolic acid-derived ligands at one axial end, and introduce -Cl or -OH groups at the other end; Alternatively, ursolic acid-derived ligands are introduced at both ends of the axial direction. The raw materials used in the preparation of this series of Pt(IV) complexes are cheap and easy to obtain, the method is simple and easy to operate, and is suitable for large-scale production. In vitro experiments show that the Pt(IV) complexes US‑CIS‑CL and US‑CIS‑OH exhibit high anticancer activity, which is superior to cisplatin, and has good selectivity for cancer cells, while being resistant to cisplatin The cancer cells also show good anticancer activity, and have the potential to be developed as a new anticancer drug with high efficiency and low toxicity and overcome cisplatin resistance.

The invention discloses an application of a class of alkaloids in reversing cisplatin resistance of lung cancer. Cisplatin (DDP) is the first-line chemotherapy drug after lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compounds TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, and TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, in which TC-1, and TD-1 not onlycan reverse drug resistance, but also enhance the sensitivity of lung cancer cells to cisplatin. A compound TB-4 does not have this effect.

The invention discloses an application of an alkaloid in preparing a drug for preventing and treating cisplatin resistance of lung cancer patients. Cisplatin (DDP) is the first-line chemotherapy drugafter lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compound TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, inwhich TC-1, TD-It not only reversed drug resistance, but also enhanced the sensitivity of lung cancer cells to cisplatin. Compound TB-It does not have this effect.

The invention discloses an alkaloid compound for preventing and treating cisplatin resistance of lung cancer patients. Cisplatin (DDP) is the first-line chemotherapy drug after lung cancer surgery. The natural and acquired drug resistance limits the efficacy of cisplatin-based combination chemotherapy. Therefore, it is necessary to develop drugs to reverse cisplatin resistance of lung cancer. As found in that present invention, compound TA-1, TA-2, TB-1, TB-2, TB-3, TC-1, TD-1, TE-1, TE-2 can effectively reverse the resistance of lung cancer cells to cisplatin, in which TC-1, TD-It not only reversed drug resistance, but also enhanced the sensitivity of lung cancer cells to cisplatin. Compound TB-It does not have this effect.

The invention provides an anti-tumor tetravalent platinum complex with anti-drug resistance function and its preparation method, the structural formula is as formula I or formula II: it is one of the following structures: the invention has excellent cytotoxicity to tumor cells activity, especially for cisplatin-resistant tumor cells, and exhibited excellent anti-tumor effect and low toxicity in vivo.