Molecular mechanism of indirubin-3＇-monoxime and Matrine in the reversal of paclitaxel resistance in NCI-H520/TAX25 cell line  

作　　者：LUO Su-xia DENG Wen-ying WANG Xin-feng LI5 Hui-fang HAN Li-li CHEN Bei-bei CHEN Xiao-bing LI Ning 

机构地区：[1]Department of Medical Oncology, Henan Tumor Hospital,Zhengzhou, Henan 450000, China

出　　处：《Chinese Medical Journal》2013年第5期925-929,共5页中华医学杂志（英文版）

摘　　要：Background Multidrug resistance （MDR） is a main reason for paclitaxel （TAX） treatment failure. Indirubin-3＇-monoxime （IRO） and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance. Methods In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520fTAX25 ceils using semi-quantitative methods. Results There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 IJmol/L for IRO and 100 IJmol/L for Matrine. So 4 tJmol/L of IRO and 100 pmol/L of Matrine were considered as the reversal dosage. When 4 IJmol/L of IRO or 100 pmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 （43.56/22.6 nmol/L） and 1.74 （43.56/25.0 nmol/L）, respectively. The mRNA expression and the protein ievel of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly （P 〈0.05） after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone. Conclusion The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.Background Multidrug resistance （MDR） is a main reason for paclitaxel （TAX） treatment failure. Indirubin-3＇-monoxime （IRO） and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance. Methods In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520fTAX25 ceils using semi-quantitative methods. Results There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 IJmol/L for IRO and 100 IJmol/L for Matrine. So 4 tJmol/L of IRO and 100 pmol/L of Matrine were considered as the reversal dosage. When 4 IJmol/L of IRO or 100 pmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 （43.56/22.6 nmol/L） and 1.74 （43.56/25.0 nmol/L）, respectively. The mRNA expression and the protein ievel of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly （P 〈0.05） after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone. Conclusion The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.

关 键 词：drug resistance PACLITAXEL indirubin-Y-monoxime Matrine 

分 类 号：Q279[生物学—细胞生物学] Q51