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.
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 humancancer. 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 humanbladder cancer cells. Firstly, Twist was found to be coexpressed with P-gp in humanbladder 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.
Authors: Andressa Ardiani; Sofia R Gameiro; Claudia Palena; Duane H Hamilton; Anna Kwilas; Thomas H King; Jeffrey Schlom; James W Hodge Journal: Cancer Res Date: 2014-02-11 Impact factor: 12.701
Authors: Yule Chen; Guodong Zhu; Kaijie Wu; Yang Gao; Jin Zeng; Qi Shi; Peng Guo; Xinyang Wang; Luke S Chang; Lei Li; Dalin He Journal: Tumour Biol Date: 2015-10-22
Authors: Sebastian Krossa; Anne Dorothée Schmitt; Kirsten Hattermann; Jürgen Fritsch; Axel J Scheidig; Hubertus Maximilian Mehdorn; Janka Held-Feindt Journal: Oncotarget Date: 2015-08-28