title: Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma.
abstract: OBJECTIVE
  This study was to investigate whether the clinically acceptable colchicine concentrations had anti-cancer effects on hepatocellular carcinoma (HCC) and their anti-cancer mechanisms.
  
  
  METHODS
  Two human HCC cell lines (HCC24/KMUH, HCC38/KMUH) and two human cancer-associated fibroblast (CAF) cell lines (F28/KMUH, F59/KMUH) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and nude mouse study using clinically acceptable colchicine concentrations.
  
  
  RESULTS
  Both 2 and 6ng/mL colchicine significantly inhibited the cellular proliferation of all cell lines tested (P<0.05). The anti-proliferative effects of colchicine on F28/KMUH, HCC24/KMUH and HCC38/KMUH cells were dose-dependent. The anti-proliferative effects of 6ng/mL colchicine on both HCC cell lines were similar to the effects of 1μg/mL epirubicin. The anti-proliferative effects of colchicine on HCC cells could be partially explained by dose-dependent up-regulations of 2 anti-proliferative genes (AKAP12, TGFB2) in these cells. TGFB2 was also up-regulated in CAFs but was not dose-dependent. Up-regulation of MX1 which can accelerate cell death was a common effect of 6ng/mL colchicine on both CAF cell lines, but 2ng/mL colchicine down-regulated MX1 in F28/KMUH cells. Nude mouse (BALB/c-nu) experiment showed that colchicine-treated mice (0.07mgcolchicine/kg/day×14days) had lower increased tumor volume ratios, slower tumor growth rates and larger percentages of tumor necrotic areas than control mice (all P<0.05).
  
  
  CONCLUSIONS
  Clinically acceptable colchicine concentrations have anti-cancer effects on HCC. This drug has potential for the palliative treatment of HCC.
authors.affiliation: Cancer Center and Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. linzuyau@yahoo.com.tw
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wu
authors.forename: Yen-Hwang
authors.initials: YH
authors.lastname: Chuang
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046228:Microarray Analysis; D064547:Myxovirus Resistance Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053781:Transforming Growth Factor beta2 / Q000235:genetics; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; D018797:Cell Cycle Proteins; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; C509041:TGFB2 protein, human; D053781:Transforming Growth Factor beta2; D050257:Tubulin Modulators; D019204:GTP-Binding Proteins; D003078:Colchicine
keywords: AKAP12; Animal study; Cancer-associated fibroblast; Colchicine; Hepatocellular carcinoma; TGFB2