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Application of compound ilamycin C and homologues thereof in preparation of drugs for treating triple negative breast cancer

A triple-negative breast cancer and compound technology, applied in the field of biomedicine, can solve the problem of unreported anti-triple-negative breast cancer activity, and achieve the effects of inhibiting proliferation and promoting apoptosis.

Active Publication Date: 2019-07-09
SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The compound ilamycin C (structure shown in the following formula) of the present invention is a known compound obtained by fermentation and purification from Streptomyces deep-sea, which is disclosed in the document "Ma J, Huang H, Xie Y, et al.Biosynthesis of ilamycins featuring Unusualbuilding blocks and engineered production of enhanced anti-tuberculosis agents.Nat Commun 2017,8,(1),391.”, but the activity of ilamycin C against triple-negative breast cancer has not been reported at home and abroad

Method used

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  • Application of compound ilamycin C and homologues thereof in preparation of drugs for treating triple negative breast cancer
  • Application of compound ilamycin C and homologues thereof in preparation of drugs for treating triple negative breast cancer
  • Application of compound ilamycin C and homologues thereof in preparation of drugs for treating triple negative breast cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The cytotoxic activity of compound ilamycin C was determined by CCK8 method. The tumor cells used in this experiment are triple-negative breast cancer cells MDA-MB-231, BT-549, non-triple-negative breast cancer cells MCF7 and normal breast cells MCF10A. Dissolve the compound ilamycin C of the present invention with dimethyl sulfoxide (DMSO) to obtain a mother solution with a concentration of 10mmol / L, and then dilute it to the required concentration with the corresponding medium of the cell line. Take the MDA-MB-231, BT-549, MCF7, MCF10A cells in the logarithmic growth phase, inoculate the cells in 96-well plates at 3000 cells / well, make 5 sub-empties for each concentration gradient, and set another 3 Set the blank hole to zero, at 37°C, 5% CO 2 Culture in the incubator for 24hrs. After the cells adhered to the wall, add the pre-prepared ilamycin C solution to each well according to the required concentration gradient, and add an equal volume of medium to the negative...

Embodiment 2

[0031] The effect of compound ilamycin C on the proliferation of triple-negative breast cells was detected by Edu kit. Take the MDA-MB-231 and BT-549 cells in the logarithmic growth phase, and use 8×10 4 cells / well, seeded in 24-well plate, at 37°C, 5% CO 2 Cultivate in the incubator for 24hrs, add the pre-prepared ilamycin C solution to each well according to the required concentration gradient, and add an equal volume of medium to the negative control well, with a total liquid volume of 500 μL per well. Set at 37°C, 5% CO 2 After culturing in the incubator for 24 hrs, dark staining was carried out according to the instructions of the Edu kit, and photographed with an inverted fluorescence microscope. Red fluorescent cells (Edu positive) represent proliferating cells. Blue fluorescence (DAPI positive) represents live cells, and the ratio (%) of proliferating cells is calculated by the ratio of red and blue fluorescence of cells using the following formula.

[0032] Prolife...

Embodiment 3

[0035] Annexin V-FITC and PI apoptosis detection kits were used for staining, and flow cytometry was used to analyze whether the compound ilamycin C had a pro-apoptotic effect on triple-negative breast cancer cells. Take the MDA-MB-231 and BT-549 cells in the logarithmic growth phase, and use 2×10 5 cells / well, seeded in 6-well plate, at 37°C, 5% CO 2 Cultivate in the incubator for 24hrs, add the pre-prepared ilamycin C solution to each well according to the required concentration gradient, add an equal volume of medium to the negative control well, and the total volume of each well is 2mL. Set at 37°C, 5% CO 2 After culturing in the incubator for 12 hrs and 24 hrs respectively, the cells were collected and added 5 μL each of Annexin V-FITC and PI, stained at room temperature for 15 min, and the cell apoptosis rate was detected by flow cytometry, and the apoptosis rate was obtained by adding the upper right quadrant and the lower right quadrant ( %).

[0036] Take the MDA-M...

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Abstract

The invention discloses application of a compound ilamycin C and homologues thereof in preparation of drugs for treating a triple negative breast cancer. According to an experiment that the compound ilamycin C influences MDA-MB-231 and BT-549 cells of the triple negative breast cancer, the compound ilamycin C has the capability of obviously inhibiting the proliferation, invasion and metastasis ofthe triple negative breast cancer and promoting the apoptosis by inhibiting the activation of an IL-6 / STAT3 pathway, so that the compound ilamycin C can be applied to the preparation of the drugs of an IL-6 / STAT3 pathway inhibitor of the triple negative breast cancer. The invention provides drug candidates for researching and developing new anti-triple negative breast cancer drugs, and a scientific basis for developing and utilizing natural active substances from deep sea microorganisms.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of compound ilamycin C and its homologues in the preparation of medicines for treating triple-negative breast cancer. [0002] Background technique: [0003] Triple-negative breast cancer refers to breast cancer that is negative for estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. Compared with other subtypes of breast cancer, the treatment of triple-negative breast cancer is still traditional chemotherapy due to the lack of effective targeted drugs. However, because triple-negative breast cancer is prone to chemotherapy resistance, its high invasion, metastasis and recurrence rates make the 5-year survival rate of patients significantly lower than that of other subtypes of breast cancer. It has been reported that the activation of IL-6 / STAT3 is related to the poor prognosis of triple-negative breast cancer, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/12A61P35/00
CPCA61K38/12A61P35/00
Inventor 马俊英张华解青鞠建华
Owner SOUTH CHINA SEA INST OF OCEANOLOGY - CHINESE ACAD OF SCI
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