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Pharmaceutical compositions and use thereof for relieving anticancer drug resistance and enhancing sensitivity of anticancer drug

A technology of pharmaceutical composition and anti-cancer drug, which is applied in the direction of drug combination, medical preparations containing active ingredients, anti-tumor drugs, etc., and can solve problems such as treatment toxicity

Pending Publication Date: 2021-05-04
RISE BIOPHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In view of this, targeted drugs did not have the expected curative effect on cancer patients, and on the contrary produced new forms of therapeutic toxicity

Method used

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  • Pharmaceutical compositions and use thereof for relieving anticancer drug resistance and enhancing sensitivity of anticancer drug
  • Pharmaceutical compositions and use thereof for relieving anticancer drug resistance and enhancing sensitivity of anticancer drug
  • Pharmaceutical compositions and use thereof for relieving anticancer drug resistance and enhancing sensitivity of anticancer drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0133] The cell lines used were Lewis lung carcinoma (LL / 2), a cell line established from the lungs of C57BL mice bearing tumors resulting from implantation of primary Lewis lung carcinoma. This lung cancer cell line was incubated at 37 °C, 5% CO 2 Grow in Dulbecco's modified Eagle's medium containing 10% FBS, 1% penicillin-streptomycin and 1% L-glutamine in a humidified cell incubator.

[0134] Human NSCLC cell lines PC9, gefitinib-resistant PC9 (PC9GR), HCC827 and gefitinib-resistant HCC827 (HCC827GR) were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin and 1% L-glutamine at 37°C with 5% CO 2in a humid cell incubator. One week after thawing the frozen GR cell line, add 3 μM gefitinib to the cells as a final concentration in the growth medium for 48 h to confirm their resistance, and then replace with fresh growth medium to maintain growth.

Embodiment 2

[0135] Embodiment 2, CXCR1, quantification of CXCR2 and CXCL8 gene expression levels

[0136] Total RNA was extracted from cells using RNA extraction reagent (REzolTM C&T, Protech Technology Enterprise Co.,) and quantified using a spectrophotometer (Nanodrop 1000, Thermo Scientific). Single-stranded cDNA was synthesized using PrimeScript RT kit (Perfect Real Time, RR037A, TAKARA Bio, Japan) and according to the user manual.

[0137] All real-time PCR reactions run through StepOnePlus TM Real-time PCR system (Applied Biosystems TM ) while using 2×qPCR BIO Probe Mix Hi-ROX reagent (PCR Biosystems, UK) and UPL probe system (IL-8, CXCR1, CXCR2). 18s as an internal control component group (internal control group, internal control). The sequences of the primers include: 5'-gagcactccataaggcaaa-3' (SEQ ID NO: 2) (forward primer of CXCL8) and 5'-atggttccttccggtggt-3' (SEQ ID NO: 3) (reverse primer of CXCL8); 5 '-gaccaacatcgcagacacat-3' (SEQ ID NO:4) (forward primer for CXCR1) and 5...

Embodiment 3

[0138] Example 3. Verification of Gefitinib-resistant cancer cell lines

[0139] In order to verify the establishment of gefitinib-resistant NSCLC cell lines, the concentration gradient of gefitinib was applied to parental cells and gefitinib-resistant cells and passed the MTT test. Gefitinib-resistant cells The drug resistance of the parental cells was 100-1000 times higher (Table 1). The IC50 value of gefitinib in PC9 cells was 0.6009 μM compared to 92.43 μM in PC9GR cells (154-fold resistance). The IC50 value of gefitinib in HCC827 cells was 0.056 μM, while that in HCC827GR cells was 125.5 μM (1517-fold resistance).

[0140] Table 1. Cytotoxicity of gefitinib in parental cells and gefitinib-resistant cell lines

[0141]

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PUM

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Abstract

Disclosed are pharmaceutical compositions and use thereof for relieving anticancer drug resistance and enhancing sensitivity of anticancer drug. Each pharmaceutical composition comprises a chemokine analogue peptide, the chemokine analogue peptide is selected from SEQ ID NO. 1; and a medicament. The medicament is selected from one or more of the targeted drugs, carriers, adjuvants, and excipients. Compared with administering targeted drugs alone, the pharmaceutical composition of the present invention can overcome the drug resistance of anti-cancer drugs, and when applied to drug-resistant cancers, the invention can increase the effect of treating cancer and inhibiting tumor growth and reduce the side effects in the process of cancer treatment, can more effectively treat cancer and inhibit tumor growth.

Description

technical field [0001] The present invention relates to a pharmaceutical composition, especially a pharmaceutical composition capable of alleviating drug resistance of anticancer drugs and increasing sensitivity of anticancer drugs and its application. Background technique [0002] With the rapid growth and aging of the global population, cancer is an increasingly prominent cause of death in many countries, representing a rapid increase in cancer incidence and mortality worldwide. [0003] Anticancer therapy is essential for cancer treatment. Cancers, on the other hand, often develop resistance to anticancer therapies. Once a cancer cell acquires resistance to an anticancer drug, the cell often displays resistance to another anticancer drug that was not used in the treatment. In other words, drug resistance is a huge problem in cancer treatment. [0004] For example, tyrosine kinase inhibitors (TKIs) are clinically the standard treatment for patients with advanced EGFR-mu...

Claims

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Application Information

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IPC IPC(8): A61K38/19A61K45/06A61P35/00A61P35/04A61P35/02
CPCA61K38/195A61K45/06A61P35/00A61P35/04A61P35/02A61K38/19A61K31/5377A61K2300/00A61K2039/505
Inventor 程家维郑锡聪游辉元徐素雅
Owner RISE BIOPHARM INC
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