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Application of euphoriafactor L1 in aspect of preparation of multidrug resistance reversal agent for tumors

A multidrug resistance technology, applied in the field of biomedicine, can solve the problems of low efficiency of tumor resistance reversal agents, lack of mechanism research, toxic effects, etc.

Inactive Publication Date: 2014-01-22
GUANGZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the main components of ABCB1-mediated tumor multidrug resistance in Echinacea Fructus are not clear yet, and its mechanism is lack of research, at present, the efficiency of using the current traditional Chinese medicine Fructus Rhizoma Fructus to prepare tumor drug resistance reversal agents is not high
Moreover, since different effective parts of Stephania chinensis may have certain toxic effects, it is difficult to obtain the effect of reversing the efflux of anticancer drugs under the condition of low-concentration medication when the reversal efficiency is not high

Method used

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  • Application of euphoriafactor L1 in aspect of preparation of multidrug resistance reversal agent for tumors
  • Application of euphoriafactor L1 in aspect of preparation of multidrug resistance reversal agent for tumors
  • Application of euphoriafactor L1 in aspect of preparation of multidrug resistance reversal agent for tumors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Leucine 1 reverses ABCB1-mediated MDR in vitro

[0031] Cells in the logarithmic growth phase were inoculated into 96-well plates, and after 24 hours of culture, different concentrations of reversal agents were added at 37 o C cultured for 1 h, and then added different concentrations of anticancer drugs. Drug resistance multiple = IC of drug-resistant cells against cancer drugs 50 Value / IC of anticancer drugs in sensitive cells 50 Value; Reversal multiple = IC of anticancer drug in cells without reversal agent 50 Value / IC of cell anticancer drug in the presence of reversal agent50 value. The results are shown in Table 1, figure 1 shown.

[0032] Table 1. The role of stepautin 1 in reversing the MDR of tumor cells mediated by ABCB1

[0033]

[0034] The above results indicate that stephacin 1 has a strong effect of reversing the MDR of tumor cells, and it can restore the sensitivity of anticancer drugs when used in combination with tra...

Embodiment 2

[0035] Example 2 Leucine 1 increases the accumulation of anticancer drugs in MDR cells

[0036] Cells in the logarithmic growth phase were inoculated into 6-well plates, and after 24 hours of culture, different concentrations of reversal agents were added at 37 o C cultured for 3 h, then added doxorubicin (DOX) at a final concentration of 10 μM for 3 h, or added rhodamine 123 (Rh123) at a final concentration of 5 μM for 30 min, collected cells, washed with ice-cold PBS for 2 h The second time, a single cell suspension was made for flow cytometry analysis. The result is as figure 2 , 3 As shown, stephacin 1 can dose-dependently increase the accumulation of anticancer drugs DOX and Rh123 in KBv200 and MCF-7 / adr cells, but has no effect on the accumulation of DOX and Rh123 in the corresponding sensitive cells KB and MCF-7 .

Embodiment 3

[0037] Example 3 Leucine 1 has no effect on the expression of ABCB1 at the mRNA and protein levels

[0038] Western blot was used to detect the protein expression level; mRNA was extracted, RT-PCR and detected by electrophoresis to analyze the mRNA expression level of ABCB1. The result is as Figure 4 As shown, auricine 1 did not affect the expression of ABCB1 at the mRNA and protein levels, suggesting that the mechanism of auricine 1 to reverse ABCB1-mediated MDR is not to reduce the expression of ABCB1.

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Abstract

The invention belongs to the field of a biological medicine, and relates to application of euphoriafactor L1 (euphoriafactor L1, EFL1) used as a multidrug resistance reversal agent for tumors, especially relates to treatment of multidrug resistance tumors by combining with antitumor drugs, so as to restore the sensitivity of tumor cells to the anti-cancer drugs. The invention also relates to a mechanism of the euphoriafactor L1 for reversing the multidrug resistance of the tumors, namely multidrug resistance (MDR) of ABCB1-mediaed tumor cells are reversed by enhancing ATP enzymatic activity of ABCB1 in the tumor cells and inhibiting an efflux function of the ABCB1; ABCB1 expression in MDR cells in messenger ribonucleic acid (mRNA) or protein level is not reduced.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to the application of Euphoria factor L1 (EFL1) in the preparation of tumor multi-drug resistance reversal agent, especially the combination treatment with anti-tumor drugs to treat multi-drug-resistant tumors, and to restore tumor cell resistance. Sensitivity to anticancer drugs, the present invention also relates to the mechanism of aurinadin 1 reversing tumor multidrug resistance. Background technique [0002] The phenomenon that tumor cells are resistant to one anticancer drug and also resistant to other anticancer drugs with different structures and different mechanisms of action is called multidrug resistance (MDR). MDR is the main reason for the failure of tumor chemotherapy, and it is also a problem that needs to be solved urgently in the field of chemotherapy. MDR is often mediated by overexpression of ATP-binding cassette (ABC) transporters, which hydrolyze ATP and use the ener...

Claims

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Application Information

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IPC IPC(8): A61K31/336A61P35/00
Inventor 张建业张超李悦山吴爱平林敏婷
Owner GUANGZHOU MEDICAL UNIV
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