title: Survivin depletion inhibits tumor growth and enhances chemosensitivity in hepatocellular carcinoma.
abstract: Survivin is a member of the inhibitor of apoptosis family, which has been suggested to be crucial in the control of cell division and inhibition of apoptosis. Expression of this protein has been observed in transformed cell lines and human tumor tissues, including those from colorectal cancer, but not in terminally differentiated adult tissues. Survivin mRNA expression has frequently been detected in hepatocellular carcinoma (HCC) and its protein expression has been demonstrated to be highly correlated with proliferation index rather than apoptotic index. The present study aimed to analyze the effect of survivin on the tumorigenicity and chemosensitivity of HCC via the establishment of an HCC cell line (PLC/PRF/5) with the stable knockdown of the survivin gene (PLC‑k3). This cell line displayed significantly lower rates of survival and proliferation in assays of cell viability and proliferation, respectively, compared with those of the control cell line (PLC‑v). In addition, PLC‑k3 cells were more sensitive to cisplatin treatment, resulting in S phase arrest. These findings were further confirmed by an in vivo experiment. The data of the present study suggest that survivin is critical in promoting cell proliferation but not in inhibition of apoptosis, and enhances the chemosensitivity of HCC. Thus, the suppression of survivin expression in combination with cisplatin may contribute to the development of more effective treatments for HCC.
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Yvonne Y Y
authors: YY
authors: Or
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Ariel K M
authors: AK
authors: Chow
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Lui
authors: L
authors: Ng
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Sheung Tat
authors: ST
authors: Fan
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Thomas C C
authors: TC
authors: Yau
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Ronnie T P
authors: RT
authors: Poon
authors: Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, P.R. China.
authors: Roberta W C
authors: RW
authors: Pang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D000077022:Survivin; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D016376:Oligonucleotides, Antisense; D000077022:Survivin; D002945:Cisplatin