Application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer)

A technology of aspirin and drugs, applied in drug combinations, antineoplastic drugs, pharmaceutical formulations, etc., can solve the problems of acquired drug resistance, absence of acquired drug resistance of osimertinib, EGFR-TKI drugs, etc., to overcome acquired drug resistance Effects of drug resistance and increased sensitivity

Inactive Publication Date: 2018-06-01
THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It has the advantages of high selectivity and low toxicity, and its role in improving the short-term and long-term curative effect and quality of life of advanced NSCLC shows encouraging prospects, but with the prolongation of treatment time, acquired drug resistance will eventually appear
Acquired drug resistance to EGFR-TKI drugs during treatment is one of the main reasons for the ineffectiveness of tumor therapy. How to solve...

Method used

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  • Application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer)
  • Application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer)
  • Application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1 In vitro experiment

[0026] The experimental steps are as follows:

[0027] (1) Amplify the two sensitive cells H1975, PC-9GR and the corresponding resistant cells H1975-OR, PC9GR-OR respectively, collect the cancer cell lines in log phase, digest the cells with trypsin, and centrifuge the cells to suspend the cells. fluid, allowing the cells to settle. Resuspend cells in medium and count;

[0028] (2) Dilute the cell density to 2×10 after counting 4 / ml, add 100 μl of cell suspension to each well of a flat-bottom 96-well plate with a sampler, each well containing 2000 cells; put the seeded 96-well plate into 5% CO 2 , overnight culture in a cell incubator at 37°C and 90% humidity;

[0029] (3) The next day, 200 mmol / L aspirin was prepared, and a concentration gradient of osimertinib was added. A total of 8 concentrations were set, and 5 replicate wells were set for each concentration. There were three groups of each cell experiment, as follows:

[0030]...

Embodiment 2

[0039] Example 2 In vitro experiment

[0040] The experimental steps are as follows:

[0041] 1. Clone Formation Experiment

[0042] (1) Sensitive cells and drug-resistant cells were digested and seeded in 6-well plates, with 500 cells per well;

[0043] (2) After culturing for 24 hours, group administration: sensitive cell control group, sensitive cell plus osimertinib group, drug-resistant cell control group, drug-resistant cell plus aspirin group, drug-resistant cell plus osimertinib group, drug-resistant cell plus aspirin group in combination with osimertinib. Aspirin (200 mmol / L), osimertinib (3 mmol / L), the control group was not treated; the culture was continued for 12 d until macroscopic clones were formed, and the medium was discarded.

[0044] (3) Immerse with phosphate buffered saline (PBS) for a short time, fix with 4% paraformaldehyde in PBS solution for 20min, then wash with PBS, stain with 0.1% crystal violet for 20min, then slowly wash away the staining solu...

Embodiment 3

[0058] Example 3 Apoptosis Experiment

[0059] The experimental steps are as follows:

[0060] (1) The H1975-OR drug-resistant cells in logarithmic growth phase were digested with 0.25% trypsin and collected in a 1.5 ml sterile centrifuge tube. The centrifuge frequency was set to 1500 r / min, and the cell solution was centrifuged for 5 min. Resuspend in RPMI 1640 medium containing 10% fetal bovine serum, count and record under a microscope with the help of a counting plate, inoculate 250,000 cells per well in a 6-well culture plate, and place in a constant temperature and humidity cell incubator Overnight, waiting for cells to attach.

[0061] (2) Take out the 6-well plate, replace 4ml of fresh medium containing 3umol / L osimol / L and / or 200umol / L aspirin, and return the 6-well plate to 37°C, 5% CO 2 The cells were incubated in a constant temperature cell incubator for 48 h.

[0062] (3) Take out the 6-well plate, digest the cells with 0.25% trypsin, collect the cells in a 1.5...

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Abstract

The invention belongs to the field of antitumor drugs and specifically discloses application of aspirin in preparing medicine for treating NSCLC (non-small cell lung cancer). In comparison with the fact that osimertinib is applied alone to treat EGFR(+) NSCLC, the drug combination of the aspirin and the osimertinib can effectively inhibit proliferation of the EGFR(+) NSCLC cells, so as to promoteapoptosis of the EGFR(+) NSCLC cells. The drug combination of the aspirin and the osimertinib enhances sensitivity of the NSCLC patient to EGFR-TKI, overcomes the defect of highly possible drug resistance to the osimertinib, increases the effective treatment time of the osimertinib and can further improve the prognosis of the EGFR(+) NSCLC patient.

Description

technical field [0001] The invention belongs to the field of tumor medicines, and particularly relates to the application of aspirin in the preparation of medicines for overcoming acquired drug resistance of osimertinib. Background technique [0002] At present, lung cancer, especially non-small cell lung cancer (NSCLC), has become a major disease threatening human health. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is currently approved in many countries and widely used in Small molecule targeted drugs targeting EGFR for advanced or refractory non-small cell lung cancer (NSCLC). At present, the first-generation EGFR-TKI drugs have been widely used in patients with advanced non-small cell lung cancer at home and abroad. It is currently available in the US, EU and China. It has the advantages of high selectivity and low toxicity, and its role in improving the short-term and long-term efficacy and quality of life of advanced NSCLC shows promising pr...

Claims

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Application Information

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IPC IPC(8): A61K31/616A61K31/506A61P35/00
CPCA61K31/506A61K31/616A61K2300/00
Inventor 何勇韩睿
Owner THE THIRD AFFILIATED HOSPITAL INST OF FIELD SURGERY OF PLA ARMY MEDICAL UNIV
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