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Use of pd-0332991 in the preparation of drugs for the prevention and treatment of drug-resistant tumors

A PD-0332991, 1. The technology of PD-0332991 is applied in the field of preparation and prevention of drug-resistant tumor drugs to achieve the effects of overcoming acquired drug resistance, preventing tumor recurrence, and overcoming drug resistance

Active Publication Date: 2018-05-01
GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In order to solve the problems existing in the prior art, the present invention provides a new application of the drug PD-0332991, which overcomes the resistance problem of the anti-tumor drug gefitinib in the prior art

Method used

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  • Use of pd-0332991 in the preparation of drugs for the prevention and treatment of drug-resistant tumors
  • Use of pd-0332991 in the preparation of drugs for the prevention and treatment of drug-resistant tumors
  • Use of pd-0332991 in the preparation of drugs for the prevention and treatment of drug-resistant tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] PD-0332991 is made into various dosage forms by adding pharmaceutically acceptable excipients according to conventional methods, such as liquid injections of various specifications, powder injections, emulsions for injections, tablets, pills, capsules, ointments, creams, patches, Liniments, powders, sprays, implants, drops, suppositories, ointments, candies, etc.

[0043] The administration routes of PD-0332991 include various administration routes: oral administration, injection administration, implant administration, intracavitary administration, sublingual administration, anal administration, transdermal administration, internal and external application, etc.

Embodiment 2

[0045] MTT assay to detect the inhibitory effect of PD-0332991 on drug-resistant tumor cells

[0046] Human lung cancer gefitinib-sensitive cell line PC-9 and gefitinib-resistant cell line PC-9 / AB2 were cultured in vitro, and the inhibitory effect of PD-0332991 on the above cells was detected by MTT assay. The results showed that PD-0332991 could effectively inhibit the growth of sensitive and drug-resistant cell lines. Figure 1-Figure 3 The dose-growth curve of gefitinib and / or PD-0332991 inhibiting the growth of gefitinib-sensitive lung cancer cell line PC-9; Figure 4-Figure 6 Dose-growth curve of gefitinib and / or PD-0332991 inhibiting gefitinib-resistant lung cancer cell line PC-9 / AB2.

Embodiment 3

[0048] Annexin V / PI double staining flow cytometry to detect cell apoptosis

[0049] PC-9 and PC-9 / AB2 cells in the logarithmic growth phase were divided into 1*10 5 Inoculate in a 6-well cell culture plate at a concentration of / ml. After the cells adhere to the wall, add PD-0332991, gefitinib, and PD-0332991 and gefitinib in combination, and set up a blank control group. After 24 hours, digest the cells with 0.25% trypsin, transfer the cell suspension into a clean test tube, centrifuge at 1000r / min for 5 minutes at 4°C to pellet the cells, discard the supernatant, wash twice with cold PBS, and resuspend the collected cells Add 5ul AnnexiV-FITC and 5ul PI to 100ul of binding buffer, mix gently, and react in the dark at room temperature for 15 minutes, add 400ul of binding buffer, and detect on the flow cytometer, the results show that PC-9 and PC-9 Under the joint action of PD-0332991 and gefitinib (PD+G), the apoptosis rate of / AB2 was significantly increased compared with ...

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Abstract

The invention discloses the use of PD-0332991 in the preparation of drugs for preventing and treating drug-resistant tumors. The present invention uses cell biology and molecular biology methods, as well as tests on human gefitinib-resistant nude mouse xenograft tumor models to prove that PD‑0332991 can effectively inhibit the growth of human gefitinib-resistant lung cancer cells and induce apoptosis. Regulates cell cycle-related genes, causes tumor cell cycle arrest, and induces apoptosis. Therefore, PD‑0332991 can be used as an active ingredient to prepare drugs for preventing and treating gefitinib-resistant tumors, as well as foods, health products and cosmetics for preventing and treating drug-resistant tumors.

Description

technical field [0001] The invention belongs to the field of medical applications, and specifically relates to the use of PD-0332991 in the preparation of drugs for preventing and treating drug-resistant tumors. Background technique [0002] The morbidity and mortality of cancer in my country are on the rise rapidly. Cancer has caused great suffering to patients and their families, and has taken up a lot of social resources and wealth. Cancer has become an increasingly serious public health problem facing mankind. However, lung cancer is the malignant tumor with the fastest increasing morbidity and mortality in my country and the greatest threat to human health and life. The overall 5-year survival rate is only about 10%. [0003] At present, the main treatment methods for lung cancer are surgery, radiotherapy, chemotherapy and biological therapy. Despite the continuous improvement of surgical techniques and the continuous marketing and clinical application of new chemothe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/5377A61P35/00A61K31/519
Inventor 陈军刘红雨刘明辉王玉丽李颖李永文
Owner GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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