Tetramethylpyrazine reverses multidrug resistance in breast cancer cells through regulating the expression and function of P-glycoprotein

被引：87

作者：

Zhang, Yinxu ^{[1
]}

Liu, Xiaomei ^{[2
]}

Zuo, Teng ^{[1
]}

Liu, Yu ^{[1
]}

Zhang, Jun Hua ^{[1
]}

机构：

[1] Liaoning Med Univ, Dept Gen Surg, Affiliated Hosp 1, Jinzhou 121001, Liaoning, Peoples R China

[2] Liaoning Med Univ, Dept Med Oncol, Affiliated Hosp 1, Jinzhou 121001, Liaoning, Peoples R China

来源：

MEDICAL ONCOLOGY | 2012年 / 29卷 / 02期

关键词：

TMP; P-glycoprotein; Multidrug resistance; Breast cancer cells; IN-VITRO;

D O I：

10.1007/s12032-011-9950-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumor multidrug resistance (MDR) has become the major obstacle to cancer chemotherapy. Recent studies suggest that tetramethylpyrazine (TMP) could reverse tumor MDR although the mechanism by which TMP overcomes tumor MDR remains elusive. Therefore, in this study, we examined the effects of TMP on MDR in drug-resistant breast cancer cells and investigated the underlying mechanisms. MCF-7 cells and the derived P-glycoprotein (Pgp) overexpressing MCF-7/dox cells were treated with TMP, and their growth was examined by MTT assay. Doxorubicin accumulation in the cells was evaluated by flow cytometry, and the expression of Pgp was detected by Western blot and RT-PCR analysis. The results showed that TMP increased the intracellular concentration of doxorubicin and inhibited Pgp-mediated efflux of doxorubicin in a dose-dependent manner. Moreover, TMP inhibited the ATPase activity of P-gp and suppressed the expression of Pgp in MCF-7/dox cells. Taken together, these data suggest that TMP has potential application in the treatment of chemotherapy-resistant breast cancer.

引用

页码：534 / 538

页数：5

共 8 条

[1] Sensitization of ABCB1 overexpressing cells to chemotherapeutic agents by FG020326 via binding to ABCB1 and inhibiting its function [J].

Dai, Chun-ling ;

Liang, Yong-ju ;

Chen, Li-ming ;

Zhang, Xu ;

Deng, Wen-jing ;

Su, Xiao-dong ;

Shi, Zhi ;

Wu, Chung-pu ;

Ashby, Charles R., Jr. ;

Akiyama, Shin-ichi ;

Ambudkar, Suresh V. ;

Chen, Zhe-sheng ;

Fu, Li-wu .

BIOCHEMICAL PHARMACOLOGY, 2009, 78 (04) :355-364

[2] The multidrug resistance of tumour cells was reversed by tetrandrine in vitro and in xenografts derived from human breast adenocarcinorna MCF-7/adr cells [J].

Fu, LW ;

Zhang, YM ;

Liang, YJ ;

Yang, XP ;

Pan, QC .

EUROPEAN JOURNAL OF CANCER, 2002, 38 (03) :418-426

[3]

Mistry P, 2001, CANCER RES, V61, P749

[4] RAPID COLORIMETRIC ASSAY FOR CELLULAR GROWTH AND SURVIVAL - APPLICATION TO PROLIFERATION AND CYTO-TOXICITY ASSAYS [J].

MOSMANN, T .

JOURNAL OF IMMUNOLOGICAL METHODS, 1983, 65 (1-2) :55-63

[5] Pharmacological strategies for overcoming multidrug resistance [J].

Nobili, S. ;

Landini, I. ;

Giglioni, B. ;

Mini, E. .

CURRENT DRUG TARGETS, 2006, 7 (07) :861-879

[6] Targeting multidrug resistance in cancer [J].

Szakács, G ;

Paterson, JK ;

Ludwig, JA ;

Booth-Genthe, C ;

Gottesman, MM .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (03) :219-234

[7] Inhibition of tetramethylpyrazine on P-gp, MRP2, MRP3 and MRP5 in multidrug resistant human hepatocellular carcinoma cells [J].

Wang, Xuan-Bin ;

Wang, Shan-Shan ;

Zhang, Qiu-Fang ;

Liu, Ming ;

Li, Hong-Liang ;

Liu, Ying ;

Wang, Jia-Ning ;

Zheng, Fei ;

Guo, Ling-Yun ;

Xiang, Ji-Zhou .

ONCOLOGY REPORTS, 2010, 23 (01) :211-215

[8] Quantitative study of the drug efflux kinetics from sensitive and MDR human breast cancer cells [J].

Zhou, Chenguang ;

Shen, Peng ;

Cheng, Yiyu .

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2007, 1770 (07) :1011-1020

← 1 →