title: Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells.
abstract: We investigated the difference in survivin expression between a multidrug-resistant lung cancer cell line (H460/cDDP) and its parental counterpart (H460) and the influence of siRNA targeting survivin on the chemosensitivity of H460/cDDP. SiRNA targeting survivin was transfected into H460/cDDP cells using a liposome approach. Survivin mRNA and protein expression were significantly higher in H460/cDDP than H460 cells. The median inhibitory concentrations (IC(50)s) for cisplatin and paclitaxol in vitro against H460/cDDP cells were significantly lower in cells treated with survivin-specific siRNA than in control cells. Apoptosis and cleaved caspase-3 expression were analysed using annexin V and Western blotting, respectively, and showed a significant increase in apoptosis after treatment with the chemotherapeutic agents plus specific siRNA. Specific siRNA sensitized H460/cDDP cells to both cisplatin and paclitaxol. Thus, survivin appears to participate in the multidrug resistance mechanism of H460/cDDP cells and siRNA targeting survivin has the potential to increase the sensitivity of drug-resistant cancer cells to anticancer drugs.
authors.affiliation: Department of Thoracic Oncology, Cancer Centre, Sun Yat-Sen University, State Key Laboratory of Oncology in Southern China, Guangzhou, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: J-H
authors.initials: JH
authors.lastname: Fu
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: W-Z
authors.initials: WZ
authors.lastname: Huang
authors.forename: B
authors.initials: B
authors.lastname: Zheng
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Wen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes / Q000737:chemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D017239:Paclitaxel / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D017239:Paclitaxel; D002945:Cisplatin