Twist Confers Chemoresistance to Anthracyclines in Bladder Cancer through Upregulating P-Glycoprotein

被引：45

作者：

Chen, Yule ^{[1
]}

Li, Lei ^{[1
,2
]}

Zeng, Jin ^{[1
]}

Wu, Kaijie ^{[1
]}

Zhou, Jiancheng ^{[1
]}

Guo, Peng ^{[2
]}

Zhang, Dong ^{[1
]}

Xue, Yan ^{[1
]}

Liang, Liang ^{[1
]}

Wang, Xinyang ^{[1
,2
]}

Chang, Luke S. ^{[1
]}

He, Dalin ^{[1
,2
]}

机构：

[1] Xi An Jiao Tong Univ, Hosp 1, Dept Urol, Xian 710061, Peoples R China

[2] Minist Educ, Key Lab Environm & Genes Related Dis, Oncol Res Lab, Xian, Peoples R China

来源：

CHEMOTHERAPY | 2012年 / 58卷 / 04期

基金：

中国国家自然科学基金;

关键词：

Twist; P-glycoprotein; Chemo-resistance; Anthracyclines; Bladder cancer; EPITHELIAL-MESENCHYMAL TRANSITION; RESISTANCE-ASSOCIATED PROTEIN; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; CELLS; CARCINOMA; MDR1; INDUCTION; CHEMOTHERAPY; MEMBRANE;

D O I：

10.1159/000341860

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Background: The membrane transporter P-glycoprotein (P-gp) was found to mediate chemoresistance, which is one of the obstacles to effective chemotherapy in several types of human cancer. The transcription factor Twist, which has been reported to participate in cancer invasion and metastasis, also plays a vital role in the progression of chemoresistance. However, the effect of Twist on P-gp-related chemoresistance remains dubious. Methods and Results: We found that Twist can regulate the expression of P-gp and then confer resistance to anthracycline drugs in human bladder cancer cells. Firstly, Twist was found to be coexpressed with P-gp in human bladder cancer cells and tissues, which were associated with enhanced chemoresistance to anthracycline drugs. Secondly, knockdown of Twist by specific siRNA treatment significantly sensitized bladder cancer cells to anthracycline drugs via inhibiting P-gp expression. Bladder cancer cells that survived transient exposure to anthracycline drugs showed higher levels of P-gp expression and more nuclear localization of Twist than untreated cells. Conclusion: We report a novel mechanism of anthracycline chemoresistance in bladder cancer in which activated Twist mediates P-gp expression in addition to its antiapoptotic roles. Therapeutic strategies targeting Twist may improve the management of recurrent bladder cancer after chemotherapy. Copyright (c) 2012 S. Karger AG, Basel

引用

页码：264 / 272

页数：9

共 42 条

[1]

Abolhoda A, 1999, CLIN CANCER RES, V5, P3352

[2]

N-cadherin gene expression in prostate carcinoma is modulated by integrin-dependent nuclear translocation of Twist1 [J].