title: Survivin-mediated therapeutic efficacy of gemcitabine through glucose-regulated protein 78 in hepatocellular carcinoma.
abstract: BACKGROUND
  Survivin is an antiapoptotic molecule that is widely expressed in cancers, including hepatocellular carcinoma (HCC). Survivin has become a general therapeutic target for cancers because of its selective overexpression in a majority of tumors. However, little is known regarding the effect of survivin expression in combination with gemcitabine on HCC.
  
  
  METHODS
  We generated survivin knockdown cells (survivin-KD) via a short interfering RNA (siRNA) technique. The antiproliferation effects of gemcitabine were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) assay, and cell cycle evaluation.
  
  
  RESULTS
  According to the MTT assay, we found that survivin-KD cells were more sensitive than parental cells and scrambled control cells to gemcitabine treatment. The apoptotic cell population increased in survivin-KD cells that were treated with gemcitabine in comparison to scrambled control cells, as observed by the cell cycle distribution and TUNEL assays. We found that survivin knockdown resulted in a reduction of glucose-regulated protein 78 (GRP78), which may be responsible for the observed increased survivin-KD cell sensitivity to gemcitabine.
  
  
  CONCLUSIONS
  We conclude that survivin knockdown may contribute to a therapeutic effect of gemcitabine through GRP78 on HCC cells.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Hung
authors.forename: Shen-Fu
authors.initials: SF
authors.lastname: Lin
authors.forename: Hui-Hsiung
authors.initials: HH
authors.lastname: Liu
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Kuo
authors.forename: Li-Tzu
authors.initials: LT
authors.lastname: Li
authors.forename: Hou-Yu
authors.initials: HY
authors.lastname: Su
authors.forename: Phui-Ly
authors.initials: PL
authors.lastname: Liew
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.forename: Der-Zen
authors.initials: DZ
authors.lastname: Liu
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D000077022:Survivin; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin; D003841:Deoxycytidine; D000093542:Gemcitabine