Pharmaceutical application of compound istradefylline for reversing drug resistance of paclitaxel

An itraphylline and drug resistance technology, which can be applied in the directions of active ingredients of heterocyclic compounds, drug combinations, and medical preparations containing active ingredients, and can solve the problem of reversing tumor drug resistance without itraphylline.

Pending Publication Date: 2021-08-10
WENZHOU MEDICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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  • Pharmaceutical application of compound istradefylline for reversing drug resistance of paclitaxel
  • Pharmaceutical application of compound istradefylline for reversing drug resistance of paclitaxel
  • Pharmaceutical application of compound istradefylline for reversing drug resistance of paclitaxel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1 Itradefylline inhibits paclitaxel-resistant non-small cell lung cancer cell proliferation in vitro

[0021] (1) Detection of the effects of different concentrations of istradefylline on the proliferation of paclitaxel-resistant non-small cell lung cancer cell lines

[0022] A549 / Taxol cells and A549 cells in the logarithmic phase were seeded in 96-well plates at a cell density of 5*10 4 / ml. The 96-well plate was placed in an incubator for 24 hours. After the cells adhered to the wall, different concentrations of paclitaxel (0.16 μM, 0.31 μM, 0.63 μM, 1.3 μM, 2.5 μM, 5.0 μM, 10 μM, 20 μM) and a fixed concentration of istradefylline (10 μM); meanwhile, a negative control group was set. After placing the 96-well plate in the incubator for 48 hours, add 20 μl of MTT working solution (5 mg / ml) to each well, continue to cultivate for 4 hours, take it out, pour off the culture solution in the 96-well plate carefully, and add 10 % dimethyl sulfoxide was shaken on ...

Embodiment 2

[0027] Example 2 Itradefylline Promotes Morphological Changes of Paclitaxel-resistant Non-small Cell Lung Cancer Cell Lines

[0028] Corresponding treatments were given according to the experimental requirements: DMSO negative control group, istradefylline group (1 μM), istradefylline group (5 μM), istradefylline group (10 μM), paclitaxel group (0.15 μM), and the above three Concentration of Itra and Paclitaxel (0.15μM) combined group respectively. After acting for 24 hours, take it out and observe it under an inverted microscope and take pictures; discard the culture medium, wash it with 1mL PBS two to three times, suck off the PBS, fix it with 4% polymethanol for 15min, and then shake it with 1mL PBS for 3 times. Add 500 μL of Hoechst 33258 dye to the wells in the dark, and incubate in the dark for 10 minutes, then wash with 1 mL of PBS shaking three times; use an inverted fluorescence microscope to observe the morphological changes of apoptotic cells and take pictures. The...

Embodiment 3

[0029] Example 3 Itradefylline Promotes Paclitaxel-resistant Non-small Cell Lung Cancer Cell Line Apoptosis

[0030] Corresponding treatments were given according to the experimental requirements, DMSO negative control group, istraphylline group (1 μM), istradefylline group (5 μM), istradefylline group (10 μM), paclitaxel group (0.15 μM), the above three Concentration of Itra and Paclitaxel (0.15μM) combined group respectively. After acting for 24 hours, digest with 0.25% trypsin (without EDTA), observe under an inverted microscope, collect the cells immediately after most of the cells are suspended, wash the cells twice with PBS, and then centrifuge at 1500rpm for 5min to collect the cells 5*10 5 Add 300 μL of Bingding Buffer to suspend the cells, add Annexin V-FITC in the dark and mix well, then add 3 μL of Propidium Iodide, mix well; react at room temperature for 15 minutes in the dark; use flow cytometry to detect cell apoptosis.

[0031] The experiment was repeated 3-4 ti...

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Abstract

The invention discloses an application of istradefylline in preparation of drugs for reversing drug resistance of tumor cells, and relates to the technical field of treatment of drug resistance of tumor cells. The istradefylline and the paclitaxel are combined to be used for preparing the medicine for reversing the drug resistance of the tumor paclitaxel. The researches find that the istradefylline can significantly reduce the expression level of MDR1 genes and proteins, and the combination of the istradefylline and the chemotherapeutic drug paclitaxel can significantly improve the sensitivity of drug-resistant cells to the chemotherapeutic drug, so that the tumor drug resistance is reversed, and the curative effect is greatly improved. Animal experiments also prove that istradefylline can effectively inhibit the growth speed of subcutaneous tumors of a drug-resistant animal model and reverse the drug resistance of paclitaxel. The results show that the istradefylline is combined with the paclitaxel, so that the treatment effect of the paclitaxel on tolerant tumors can be effectively enhanced. The condition that many malignant tumor cells have drug resistance to paclitaxel is clinically found, and therefore istradefylline has good development value and application prospects.

Description

technical field [0001] The invention relates to a new medical application of istradefylline, in particular to the application of istradefylline in reversing tumor drug resistance to paclitaxel, and belongs to the technical field of tumor cell drug resistance treatment. Background technique [0002] Lung cancer, breast cancer, pancreatic cancer, gastric cancer, etc. are the main types of cancers that cause cancer-related deaths worldwide. The standard treatment methods for these tumors include surgical resection, chemotherapy and radiation therapy. Since most cancer patients are found to be in the advanced stage of cancer, chemotherapy It is considered the backbone of the treatment of cancer. Paclitaxel is an anti-mitotic agent of taxanes. Due to its good tumor killing effect, it has been used clinically for many years as a first-line treatment for lung cancer, breast cancer, pancreatic cancer, gastric cancer and other cancers. However, after a period of treatment, tumor cel...

Claims

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Application Information

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IPC IPC(8): A61K31/522A61P35/00A61K31/337
CPCA61K31/522A61K31/337A61P35/00A61K2300/00
Inventor 王学宝叶发青高国辉孙豆豆鲁颖叶辉张园左志贵刘志国谢自新
Owner WENZHOU MEDICAL UNIV
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