Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma

Aims: This study was to investigate whether the clinically acceptable colchicine concentrations had anticancer effects on hepatocellular carcinoma (HCC) and their anti-cancer mechanisms. Main 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. Key findings: Both 2 and 6 ng/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 6 ng/mL colchicine on both HCC cell lines were similar to the effects of 1 mu g/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 6 ng/mL colchicine on both CAF cell lines, but 2 ng/mL colchicine down-regulated MX1 in F28/KMUH cells. Nude mouse (BALB/c-nu) experiment showed that colchicine-treated mice (0.07 mg colchicine/kg/day x 14 days) had lower increased tumor volume ratios, slower tumor growth rates and larger percentages of tumor necrotic areas than control mice (all P < 0.05). Significance: Clinically acceptable colchicine concentrations have anti-cancer effects on HCC. This drug has potential for the palliative treatment of HCC. (C) 2013 Elsevier Inc. All rights reserved.