Unsaturated lactone ingredient and chemotherapy drug composition and application thereof

A technology for chemotherapeutic drugs and compositions, applied in the field of medicine, can solve the problems of reduced accumulation, cisplatin resistance, complexity and the like

Inactive Publication Date: 2016-02-03
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The mechanism of tumor resistance to platinum is very complex, and the currently discovered drug resistance mechanisms mainly include the following aspects: the reduction of cisplatin accumulation in cells; the excessive influx and passivation of sulfhydryl molecules such as GSH all lead to cell Drug resistance to cisplatin; excessive clearance of cisplatin adducts in the DNA repair pathway can also lead to drug resistance to cisplatin; misexpression of signaling pathway regulatory proteins related to the control of apoptosis pathways can also affect the ability of cisplatin platinum sensitivity
Therefore, the complexity of the mechanism of tumor resistance to cisplatin is still a "bottleneck" problem in the research and development of tumor resistance reversal agents.
[0005] At present, although some compounds have shown the reversal effect on tumor drug resistance, the toxic side effects of these compounds limit their clinical application

Method used

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  • Unsaturated lactone ingredient and chemotherapy drug composition and application thereof
  • Unsaturated lactone ingredient and chemotherapy drug composition and application thereof
  • Unsaturated lactone ingredient and chemotherapy drug composition and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0022] After crushing the medicinal material of inulin, extract three times with 95% ethanol, recover ethanol, suspend the obtained extract with appropriate amount of water, extract five times with petroleum ether, recover petroleum ether, and obtain petroleum ether extract.

[0023] Column chromatographic separation: the petroleum ether extract is separated by silica gel column chromatography, and purified by eluting with petroleum ether-ethyl acetate to obtain inulin and isoinuractone.

Embodiment 2

[0025] Inhibition of the growth of ovarian cancer cells by the compounds inulin and iso-inulin in combination with cisplatin.

[0026] Take the OVCAR-3 cells in the logarithmic growth phase and add them to a 96-well plate, 9×10 per well 3 After 24 hours of culture, the inulin and isoearwood lactone were combined with different concentrations of cisplatin. After 24 hours of action, 20 μL of MTT (5 mg / mL) solution was added to each well, and the culture was continued for 4 hours, and the supernatant was removed. Add 100 μL DMSO to each well, and measure the OD value at 570 nm with a microplate reader. For the synergistic effect of the combination of inulin and isoinulin and cisplatin (30μM), see figure 1 .

Embodiment 3

[0028] Effects of inulin and iso-inulin in combination with cisplatin in inducing apoptosis in ovarian cancer cells.

[0029] Take the OVCAR-3 cells in the logarithmic growth phase, add them to a 6-well plate, and wait until the cell growth density is 70%, add drugs to treat for 24 hours, remove the medium, carefully rinse the adherent cells in the wells twice with PBS, and remove the remaining Wash the culture medium, and try not to lose the adherent cells. After rinsing, place it on an ultra-clean bench to dry naturally. Add freshly prepared cell fixation solution (methanol: glacial acetic acid = 3:1 (v / v)), add 500 μL to each well, and after standing at room temperature for 10 min, remove the fixation solution and let it dry naturally. Add freshly prepared Hoechst staining solution (5 μg / mL) for staining, add 300 μL to each well, and keep away from light. After staining for 45 minutes, remove Hoechst staining solution, wash away the remaining staining solution with PBS, ke...

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Abstract

The invention discloses an unsaturated lactone ingredient and anti-tumor chemotherapy drug composition and medical application thereof. The invention provides unsaturated lactone ingredients extracted from natural plants, on the condition without obvious cytotoxicity dosage, these ingredients are combined with platinum chemotherapy drugs to have a collaborative anti-tumor effect and reverse a drug resistance effect of tumors to the platinum drugs.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a combination of unsaturated lactone components and platinum chemotherapy drugs and its medical application. Background technique [0002] Malignant tumors are the number one killer threatening human health, causing 7.6 million deaths in 2008 (about 13% of all deaths), and about 70% of cancer deaths occurred in low- and middle-income countries. Cancer deaths worldwide are projected to continue to rise, exceeding 13.1 million by 2030. [0003] Chemotherapy is currently one of the most important means of treating malignant tumors clinically. However, due to the resistance of tumor cells to chemotherapeutic drugs, chemotherapy fails in patients. Platinum chemotherapeutic drugs (cisplatin, carboplatin, oxaliplatin) are widely used in the treatment of various cancers, and their anticancer mechanism has not been fully studied. At present, it is generally believed that pl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/24A61K47/22A61P35/00
Inventor 余建清雷嘉川李洁
Owner WUHAN UNIV
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