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Application of Schizandrin A on curing drug resistance for multiple drugs of treating tumors

A schisandrin A, multi-drug resistance technology, applied in the direction of anti-tumor drugs, drug combinations, ether/aldol active ingredients, etc., can solve the toxic and side effects, cardiovascular toxicity, and unsatisfactory effect of solid tumor resistance reversal and other problems, to achieve a significant dose-dependent, strong reversal effect

Inactive Publication Date: 2005-03-30
CHANGCHUN JILIN UNIV HI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, many compounds have been found to have strong tumor multidrug resistance reversal effects in vitro and in vivo animal experiments, such as calcium channel blockers including verapamil, calmodulin antagonists, cyclosporins, Quinolines and anti-estrogens, however, when used clinically, in addition to the relatively certain reversal effect on some blood system tumor drug resistance, the reversal effect on solid tumor drug resistance is not ideal
It is generally believed that these compounds cannot achieve an effective reversal concentration in the body at a dose that can be tolerated by the human body, and once the dose is increased to make the blood drug concentration reach the concentration with reversal activity in the in vitro test, serious toxic and side effects will occur. Or when reversal agents are used in combination with antineoplastic drugs, the pharmacokinetic parameters of antineoplastic drugs will be changed, resulting in unforeseen toxic and side effects
For example, verapamil as a positive control in the present invention has strong tumor resistance reversing activity in vitro, but it is found that cardiovascular toxicity is produced when it does not reach the concentration of reversing drug resistance when applied to the body, thus limiting its clinical use

Method used

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  • Application of Schizandrin A on curing drug resistance for multiple drugs of treating tumors
  • Application of Schizandrin A on curing drug resistance for multiple drugs of treating tumors
  • Application of Schizandrin A on curing drug resistance for multiple drugs of treating tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Take KB, KBv200, MCF-7, MCF-7 / Adr, Bel in logarithmic growth period 7402 The cells were seeded in a 96-well culture plate (Coster). After 24 hours of culture, gradient concentrations of anticancer drugs, reversal agents and control solvents were added. Continue to incubate for 72 hours, then discard the culture medium, add 0.5 mg / ml thiazolyl (MTT) 100μl to each well (diluted with serum-free RPMI 1640 medium), continue to incubate for 4 hours, discard thiazolyl, and add to each well 150μl of dimethyl sulfoxide, slightly shake to dissolve the precipitate, and measure the absorbance at 570nm in a microplate reader (Bio-Rad 450 type). Set three to four multiple holes in each group to take the average value and calculate IC 50 . 10μmol / L verapamil was used as a positive control. The specific results are shown in Table 1-10.

[0050] Table 1. The effect of schisandrin A on the sensitivity of KBv200 thin breast to vincristine

[0051] Drug Concentration Cell Survival Half of Vinc...

Embodiment 2

[0139] Take the logarithmic growth period Bel 7402 When the cells are 70-80% of the bottom of the bottle, replace the RPMI 1640 culture medium containing 10μmol / L of adriamycin, and add the final concentration of 50, 25μmol / L Schisandrin, and 10μmol / L Vera Pamir was used as a positive control, with three parallel samples in each group, 37°C, 5% CO 2 Continue to incubate for 3 hours, wash three times with ice-cold PBS (pH 7.4), collect the cells, take a certain number of cells, suspend the cells in 1.2ml hydrochloric acid (0.3N)-ethanol (50%), and break the cells on a sonicator After centrifugation at 10,000 rpm for 15 minutes, take 1.0 ml of the supernatant and add 2.0 ml of the above-mentioned hydrochloric acid-ethanol solution, and measure the fluorescence value of adriamycin with a fluorescence spectrophotometer. The excitation wavelength is 470nm and the emission wavelength is 580nm. Calculation of content-fluorescence standard curve10 6 The content of adriamycin in each cell....

Embodiment 3

[0141] Vaccination of KB, KBv200 and Bel 7402 Cells were placed on a culture dish with a diameter of 3.5 cm and cultured for 24 hours. After washing away the non-adherent cells, rhodamine 123 (final concentration of 250 ng / ml) and / or schisandrin A of different concentrations were added respectively. The control group only added Schisandrin A. After incubating for 30 minutes at room temperature, the cells were washed twice with 0.1M phosphate buffer, and the accumulation of rhodamine 123 in the cells was observed by a laser scanning confocal microscope. Each petri dish was randomly selected from 5 visual fields for observation, and the average fluorescence intensity was analyzed by computer software. At least 50 cells are analyzed for each sample. The main parameters of each petri dish in the image processing are the same. See the result figure 2 , 3 .

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Abstract

An application of schisandrin A in treating the drug-resistant tumor is disclosed. It can be used in conjunction with antineoplastic for increasing the sensitivity of tumor to antineoplastic.

Description

Technical field [0001] The present invention relates to a new use of schisandrin A as a multidrug resistance reversal agent, especially when combined with an antitumor drug to treat tumors with multidrug resistance, and to improve the sensitivity of tumor cells to anticancer drugs. The present invention also relates to schisandra anti New uses for tumors. Background technique [0002] The acquired drug resistance of tumor cells after chemotherapy and the inherent drug resistance of some tumor cells are still one of the important reasons for the failure of tumor chemotherapy. The mechanism of multidrug resistance is very complicated. The overexpression of multidrug resistance glycoprotein (P-gp) existing on tumor cell membrane is the main mechanism. Many chemotherapeutics are substrates of P-gp, such as vinblastine. , Anthracyclines, epipodophyllotoxins, taxanes, etc. Reversing the multidrug resistance of tumor cells so that the tumor cells can restore their sensitivity to chemoth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/09A61P35/00
Inventor 刘耕陶黄敏金晶魏怀玲孙华
Owner CHANGCHUN JILIN UNIV HI TECH
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