Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells

Zhu,Kexiu; Chen,Lihong; Han,Xiaobing; Wang,Jia; Wang,Jue

doi:10.3892/or.2012.1633

Short hairpin RNA targeting Twist1 suppresses cell proliferation and improves chemosensitivity to cisplatin in HeLa human cervical cancer cells

Authors:
- Kexiu Zhu
- Lihong Chen
- Xiaobing Han
- Jia Wang
- Jue Wang
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Affiliations: Department of Obstetrics and Gynecology, First Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, The Key Laboratory of Biomedical Information Engineering of the Ministry of Education, Research Center of Rehabilitation Science and Technology, School of Life Science and Technology, Xi'an Jiaotong University, 28 Xian Ning West Road, Xi'an, Shaanxi 710049, P.R. China
Published online on: January 12, 2012 https://doi.org/10.3892/or.2012.1633
Pages: 1027-1034

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Abstract

Development of multidrug resistance (MDR) remains a major hurdle to successful cancer chemotherapy and MDR1/P-gp overexpression is believed to be mainly responsible for MDR of tumor cells. Twist1, which is a highly conserved transcription factor that belongs to the family of basic helix-loop-helix proteins, has been shown to be a major regulator of the epithelial-mesenchymal transition (EMT), and therefore promotes carcinoma metastasis. Recently, a novel function of Twist1 was reported to confer radioresistance or chemoresistance in cervical cancer. However, mechanisms of such efficacy are not completely elucidated. In the present study, we firstly analyzed the relationship between Twist1 and MDR1/P-gp expression in human cervical cancer specimens and demonstrated a positive correlation between Twist1 and MDR1/P-gp expression in the same patient. Additionally, we provide the first evidence that silencing of Twist1 by RNAi downregulated MDR1/P-gp expression in HeLa cervical cancer cells, suppressed the cell proliferation, inhibited Rhodamine123 efflux activity of cells and sensitized cells to cisplatin treatment. Collectively, these ﬁndings suggest that Twist1-mediated modulation of MDR1/P-gp expression plays an important role in sensitization of cervical cancer cells to cisplatin, and also indicate a novel therapeutic strategy to overcome drug resistance through inactivation of Twist1 expression in cervical cancer.

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