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Combined preparation and application of combined preparation in preparing non-small-cell lung carcinoma drug

A non-small cell lung cancer and preparation technology, which is applied in drug combinations, antineoplastic drugs, and pharmaceutical formulations, can solve drug resistance and other problems, and achieve the effect of inhibiting proliferation

Active Publication Date: 2013-10-02
WUHAN INST OF PHYSICS & MATHEMATICS CHINESE ACADEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is the problem that patients with non-small cell lung cancer are prone to drug resistance to EGFR tyrosine kinase inhibitory drugs during treatment

Method used

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  • Combined preparation and application of combined preparation in preparing non-small-cell lung carcinoma drug
  • Combined preparation and application of combined preparation in preparing non-small-cell lung carcinoma drug
  • Combined preparation and application of combined preparation in preparing non-small-cell lung carcinoma drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Using RNA interference technology to increase the concentration of GSH in lung cancer cells (cells referred to below refer to lung cancer cells)

[0027] (1) Materials and methods of cell experiments

[0028] Using RNA interference technology (siRNA) to inhibit the expression of genes related to GSH decomposition (GGT1, GPX1, GSTpi) and GSH synthesis related genes (GSS, GCLC, GSR) to regulate the GSH content in cells. siRNA transfection was completed using RNAiMax (Invitrogen) reagent according to the instructions.

[0029] After using RNA interference technology to increase the GSH content in cells, 50nM Erlotinib was used.

[0030] (2) Results

[0031] When the RNA interference technology is used to inhibit the genes related to GSH decomposition in cells (GGT1, GPX1, GSTpi), the sensitivity of PC9 and PC9ER to Erlotinib will increase, such as figure 2 As shown in A, when GGT1 is inhibited, the relative survival number of cells is reduced by about 30%, w...

Embodiment 2

[0032] Example 2: Using drug intervention to increase the content of GSH in cancer cells

[0033] (1) Materials and methods

[0034] Lung cancer cells were treated with glutathione S-transferase inhibitor Ethacrynic acid (EA) and glutathione peroxidase (GPXs) inhibitor mercaptosuccinate (MS). The concentrations of EA and MS used were both 50 μM. After 48 hours of action, the survival rate of the cells and the GSH content in the cells were measured by the method described above.

[0035] (2) Results

[0036] Such as image 3 As shown in A, PC9ER cells resistant to EGFR tyrosine kinase inhibitors are resistant to Erlotinib (Erlo) alone, but are sensitive to the combination of Erlo and EA, and the combination of Erlo and EA reduces the survival rate of drug-resistant lung cancer cells Significantly lower than Erlo alone administration group, EA alone does not have anti-cancer effect; image 3 As shown in B, the result of combined drug use on drug-resistant H1975 cells is cons...

Embodiment 3

[0039] Example 3: Combined action of EGFR tyrosine kinase inhibitors and diuretic acid inhibits the growth of drug-resistant tumors in nude mice

[0040] (1) Materials and methods

[0041] EGFR tyrosine kinase inhibitor drug-resistant lung cancer cell PC9ER was divided into 5×10 6 The number of cells inoculated subcutaneously in the armpit of BALB / c nude mice, when the tumor volume is 100mm 3 Dosing was started, 10 rats in each group. The selected EGFR tyrosine kinase inhibitor is Erlotinib (Erlo), and the drug to increase the GSH content in lung cancer cells is diuretic acid (EA). The dosage is equivalent to the level of clinical medication, Erlo is 25mg / kg body weight / day, EA is 6.25mg / kg body weight / day, and the administration method is intraperitoneal injection. The tumor size was measured every four days with a vernier caliper, and the GSH content in the tumor was measured with a GSH kit (BioAssay Systems) after the experiment.

[0042] (2) Results

[0043] Such as ...

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Abstract

The invention discloses a combined preparation and an application of the combined preparation in preparing a non-small-cell lung carcinoma drug. An EGFR (Epidermal Growth Factor Receptor) tyrosine kinase inhibitor and a preparation for increasing a concentration of glutathione (GSH) in lung carcinoma cells are administered simultaneously or successively. According to the combined preparation and the application, through a systemic research, the GSH plays an important role in resisting the EGFR tyrosine kinase inhibitor to an EGFR T790M mutation non-small-cell lung carcinoma, so that drug resisting cells are sensitive to treatment of the EGFR tyrosine kinase inhibitor again by utilizing a mode of increasing the concentration of the GSH in the lung carcinoma cells; and a cell experiment and an animal experiment prove that the method is safe and effective, can effectively kill the lung carcinoma cells, and can inhibit proliferation of the lung carcinoma cells.

Description

technical field [0001] The invention relates to the field of non-small cell lung cancer treatment, in particular to a combination preparation and its application in the preparation of non-small cell lung cancer drugs, which are used to re-sensitize drug-resistant cells to the treatment of EGFR tyrosine kinase inhibitor drugs. Background technique [0002] Lung cancer is one of the most common cancers in humans. According to the results of the third national cause of death survey released by the National Health and Family Planning Commission (formerly the Ministry of Health) on April 29, 2008, lung cancer replaced liver cancer as the first cause of death from malignant tumors in my country. Non-small cell lung cancer (NSCLC, Non-small-cell carcinoma) accounts for about 85% of the total number of lung cancers (Molina, J.R. et al., Mayo Clinic Proceedings2008, 83(5), 584-594), and non-small cell lung cancer is very prone to occur Metastasis thus causes multiple complications re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/192A61K31/194A61P35/00A61P11/00
CPCA61K31/192A61K31/517A61K45/06A61P11/00A61P35/00A61K2300/00
Inventor 唐惠儒李洪德奥利费·埃曼纽尔·拉菲·普拉多王玉兰麦克尔·朱利安·赛克尔
Owner WUHAN INST OF PHYSICS & MATHEMATICS CHINESE ACADEMY OF SCI
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