title: Short hairpin RNA targeting Twist1 suppresses cell proliferation and             improves chemosensitivity to cisplatin in HeLa human cervical cancer cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, First Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China.
authors.forename: Kexiu
authors.initials: K
authors.lastname: Zhu
authors.forename: Lihong
authors.initials: L
authors.lastname: Chen
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Han
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D002945:Cisplatin