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Application of methidazine in improving progestogen resistance of endometrial cancer

A technology of endometrial cancer and thioridazine is applied in the application field of thioridazine in improving progesterone resistance of endometrial cancer, which can solve problems such as drug resistance, achieve improving progesterone resistance, promoting The effect of inhibiting proliferation and promoting apoptosis

Inactive Publication Date: 2019-03-29
THE INT PEACE MATERNITY & CHILD HEALTH HOSPITAL OF CHINA WELFARE INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, the conservative treatment for patients with endometrial cancer and precancerous lesions (complex dysplasia) who have the need to preserve reproductive endocrine function is progesterone therapy. Literature [Wei J, Zhang W, Feng L, Gao W. Comparison Of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: A meta-analysis and systematic review. Medicine (Baltimore). 2017.96(37): e8034.], it was reported that progesterone treatment of early endometrial cancer completely Response rate was only 71%, and up to 33% of patients who were initially sensitive to progesterone therapy developed resistance to subsequent treatment

Method used

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  • Application of methidazine in improving progestogen resistance of endometrial cancer
  • Application of methidazine in improving progestogen resistance of endometrial cancer
  • Application of methidazine in improving progestogen resistance of endometrial cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1. The experiment of thioridazine combined with medroxyprogesterone acetate inhibiting the proliferation and viability of endometrial cancer cells

[0025] The materials are as follows:

[0026] Cells: endometrial cancer cell lines Ishikawa, KLE; drugs: thioridazine, medroxyprogesterone acetate (MPA)

[0027] Method: Cells in the logarithmic growth phase with a density of 8×103 cells / well were inoculated in a 96-well plate for culture. After 24 hours, different concentrations of MPA (0, 1, 10, 20, 30, 40, 50 μmol / L) were added. Concentration gradients were used to set 6 parallel wells, and then placed in a 37° C., 5% CO2 incubator for 24 hours to conduct experiments.

[0028] The cells in the logarithmic phase of growth were collected, and the drugs were divided into groups according to the experiment. Six parallel wells were set up in each group, and they were cultured for 1, 2, 3, and 4 days respectively for the experiment. Calculate the inhibition rate of...

Embodiment 2

[0030] Example 2. The experiment of thioridazine combined with medroxyprogesterone acetate inhibiting the apoptosis of endometrial cancer cells

[0031] The materials are as follows:

[0032] Method: The cells in the logarithmic growth phase were routinely digested. After 24 hours of inoculation, the cells were replaced with serum-free medium and cultured for 18 hours. After adding the experimental drug for 72 hours (drug treatment grouping was the same as in Example 1), conventional EDTA-free trypsin digestion was used, and cold PBS was used. buffer to wash the cells twice, and then make 1×10 with 1×Binding Buffer 6 For single cell suspension, centrifuge to discard the supernatant, then wash twice with pre-cooled phosphate buffered saline (PBS), add 100 μl of cell suspension to the Falcon test tube, add AnnexinV-FITC and 5 μl of accounting dye (PI) respectively , mixed gently, and placed in a dark place at room temperature for 15 minutes. Add 400 μl of 1×Binding Buffer to...

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Abstract

The invention discloses an application of methidazine in improving progestogen resistance of endometrial cancer; with single use of methidazine, the proliferation and viability of endometrial cancer cells are inhibited; or with combined use of methidazine and progestogen, the killing effect of progestogen on progestogen-resistant endometrial cancer cells is promoted. The methidazine is found out to inhibit the proliferation and viability of progestogen-sensitive / insensitive endometrial cancer cells and have no influence on apoptosis of the endometrial cancer cells; with combined use of methidazine and progestogen (MPA), the proliferation inhibition and apoptosis promotion effects of the progestogen on the progestogen-sensitive / insensitive endometrial cancer cells are further promoted.

Description

technical field [0001] The invention relates to medicinal chemistry, in particular to the application of thioridazine in improving progesterone drug resistance of endometrial cancer. Background technique [0002] Thioridazine is an antipsychotic drug that acts on the central nervous system, autonomic nervous system and endocrine system. Literature [Sachlos E, RM, Laronde S, Shapovalova Z, Lee JH, Russell J, Malig M, McNicol JD, Fiebig-Comyn A, Graham M, Levadoux-Martin M, Lee JB, Giacomelli A, Hassell JA, Fischer-Russell D, Trus MR, Foley R , Leber B, Xenocostas A, Brown ED, Collins TJ, Bhatia M.Identification of drugs including a dopamine receptorantagonist that selectively target cancer stem cells. Darzine can inhibit the carcinogenesis of leukemia stem cells in vivo by inhibiting the dopamine receptors expressed on the surface of tumor stem cells and breast cancer cells. But there is no report that the drug can increase progesterone sensitivity. [0003] At present, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/5415A61K31/57A61P35/00
CPCA61K31/5415A61K31/57A61P35/00A61K2300/00
Inventor 王玉东孙笑王晶孟琼
Owner THE INT PEACE MATERNITY & CHILD HEALTH HOSPITAL OF CHINA WELFARE INST