Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells.
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.
Yang
H
H
Department of Thoracic Oncology, Cancer Centre, Sun Yat-Sen University, State Key Laboratory of Oncology in Southern China, Guangzhou, PR China.
Fu
J-H
JH
Hu
Y
Y
Huang
W-Z
WZ
Zheng
B
B
Wang
G
G
Zhang
X
X
Wen
J
J
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
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