title: Anti-cancer effects of p21WAF1/CIP1 transcriptional activation induced by dsRNAs in human hepatocellular carcinoma cell lines.
abstract: OBJECTIVE
  To investigate the anti-cancer effects of p21WAF1/CIP1 transcriptional activation induced by dsRNAs in hepatocellular carcinoma (HCC) cell lines.
  
  
  METHODS
  HCC cell lines BEL7402, SMMC-7721, MHCC97L, MHCC97H, and MHCCLM3 were used. HCC cells were treated with dsP21-322 (50 nmol/L), dsControl (50 nmol/L), siP21 (50 nmol/L), or mock transfection. The expression of p21 was detected using quantitative PCR and Western blot. The effects of RNA activation on HCC cells were determined using cell viability assays, apoptosis analyses and clonogenic survival assays. Western blot was also conducted to detect the expression of Bcl-xL, survivin, cleaved caspase-3, cleaved caspase-9 and cleaved PARP.
  
  
  RESULTS
  At 72 to 120 h following the transfection, dsP21-322 markedly inhibited the viability of HCC cells and clone formation. At the same times, dsP21-322 caused a significant increase in HCC cell apoptosis, as demonstrated with cytometric analysis. The phenomena were correlated with decreased expression levels of the anti-apoptotic proteins Bcl-xL, surviving, and increased expression of cleaved caspase-3, cleaved caspase-9 and cleaved PARP.
  
  
  CONCLUSIONS
  RNA-induced activation of p21 gene expression may have significant therapeutic potential for the treatment of hepatocellular carcinoma and other cancers.
authors.affiliation: Department of Surgery, Jinshan Hospital, Fudan University, Shanghai 200540, China.
authors.forename: Zhi-ming
authors.initials: ZM
authors.lastname: Wu
authors.forename: Chun
authors.initials: C
authors.lastname: Dai
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Cui-fang
authors.initials: CF
authors.lastname: Zheng
authors.forename: Qiong-zhu
authors.initials: QZ
authors.lastname: Dong
authors.forename: Guan
authors.initials: G
authors.lastname: Wang
authors.forename: Xiao-wen
authors.initials: XW
authors.lastname: Li
authors.forename: Xiao-fei
authors.initials: XF
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D012330:RNA, Double-Stranded / Q000235:genetics / Q000627:therapeutic use*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012330:RNA, Double-Stranded; D053148:Caspase 3; D053453:Caspase 9