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Medicinal composition having tumor-resistant synergy

An anti-tumor drug, synergistic technology, applied in the direction of anti-tumor drugs, drug combinations, medical preparations containing active ingredients, etc., to achieve a significant tumor inhibitory effect

Inactive Publication Date: 2010-08-25
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the present invention, the enediyne antitumor antibiotic Lidamycin and Anza-type geldanamycin are used in combination to synergistically increase sensitivity and improve the antitumor effect. There has been no relevant report so far.

Method used

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  • Medicinal composition having tumor-resistant synergy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Synergistic inhibitory effect of lidamycin and geldanamycin on SKOV-3, MCF-7 and Bel-7402 cells

[0056] The above cells in the logarithmic growth phase were digested, counted, and spread on a 96-well plate. After 24 hours, different concentrations of drugs were added, and the culture was continued for 72 hours. MTT (tetrazolium blue) was added, incubated at 37°C for 4 hours, and DMSO was added. (dimethyl sulfoxide) to dissolve the blue-purple particles, and measure the absorbance at 570 nm in each well on a microplate reader. The OD value of each test well was subtracted from the background OD value (complete medium plus MTT, no cells), and the OD value of each parallel well was averaged. The survival rate of the cells is represented by T / C (%), T is the OD value of the drug-treated cells, and C is the OD value of the control cells. Cell viability%=(medicated cell OD-background OD) / (control cell OD-background OD)×100%.

[0057] Calculate the interaction coefficient...

Embodiment 2

[0059] Hsp90 inhibitor enhances the effect of lidamycin-induced apoptosis

[0060] In normal living cells, phosphatidylserine (phosphotidylserine, PS) is located on the inner side of the cell membrane, and once apoptosis is initiated, PS becomes an early apoptosis signal. Annexin V is a Ca with a molecular weight of 35-36kD 2+ Dependent phospholipid-binding protein, in the process of apoptosis, can specifically bind with high affinity to PS that is exposed to the extracellular environment from the inside of the cell membrane to the surface of the cell membrane. Propidiumiodide (PI) is a nucleic acid dye that cannot penetrate the intact cell membrane, but it can penetrate the intact cell membrane and stain red in the late stage of apoptosis and dead cells. Annexin V is labeled with FITC fluorescein as a fluorescent probe and used in combination with PI to distinguish living cells, early apoptotic cells, late apoptotic cells, and dead cells.

[0061] The Annexin V Cell Apoptos...

Embodiment 3

[0075] Hsp90 inhibitors enhance the ability of lidamycin to cleave DNA by inhibiting post-DNA repair repair.

[0076] Cells were pretreated with geldanamycin for 16 hours and then treated with lidamycin for different times. γH2AX is one of the earliest proteins bound to DNA double-strand breaks, and the amount of γH2AX is usually used to indicate the degree of DNA double-strand breaks. The level of intracellular γH2AX was detected by immunofluorescence, and the operation was as follows:

[0077] 1) Inoculate cells in a 6-well cell culture plate;

[0078] 2) 37°C environment with 5% CO 2 Cultivate in the incubator of concentration for 24h;

[0079] 3) According to the needs of the experiment, the cells were treated with drugs at different times, lidamycin and geldanamycin or a combination of the two;

[0080] 4) Wash 3 times with PBS, 5 minutes each time;

[0081] 5) Fix with 4% paraformaldehyde for 30 minutes;

[0082] 6) Wash 3 times with PBS, 5 minutes each time;

...

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Abstract

The invention relates to a medicinal composition having tumor-resistant synergy. The composition consists of a lidamycin olefin diyne type antibiotic, a geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof. Research shows that the geldanamycin benzoquinone ansamycin type antibiotic and derivatives thereof, which serve as a chemical therapy sensitivity enhancer, can inhibit the restoration of the DNA damaged by DNA damage medicaments, and achieve a synergic effect for treating tumor when used in combination with the chemical therapy medicament of the lidamycin olefin diyne type antibiotic.

Description

Technical field: [0001] The invention relates to a pharmaceutical composition with anti-tumor synergistic effect, in particular to a therapeutic drug for inhibiting post-damage DNA repair. Background technique: [0002] Post-damage DNA repair is one of the important mechanisms for tumor cells to develop resistance to DNA-damaging agents. Inhibiting the repair ability after DNA damage can well enhance the efficacy of DNA damage agents. As a DNA damage drug, lidamycin can induce post-damage repair in cells. Lidamycin will activate the post-damage repair process of DNA when it breaks DNA. If the dose of lidamycin used is relatively low, the resulting DNA damage can be repaired under the action of cellular DNA repair enzymes, and tumor cells can continue to survive. Therefore, finding a drug that can reduce the repair ability of DNA damage in cells and using lidamycin at the same time can enhance the tumor killing effect of lidamycin and reduce the dosage of lidamycin. [000...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K38/16A61K31/395A61P35/00
Inventor 韩菲菲甄永苏李良吴淑英刘秀均
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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