title: Clinically acceptable colchicine concentrations have potential for the palliative treatment of human cholangiocarcinoma.
abstract: Microtubules are an ideal target for anticancer drugs because of their essential role in mitosis. Colchicine is a microtubule destabilizer. Whether the clinically acceptable colchicine concentrations had anticancer effects on human cholangiocarcinoma cells was investigated. Two human cholangiocarcinoma cell lines (C14/KMUH, C51/KMUH) were investigated using clinically acceptable plasma colchicine concentrations (2 ng/mL and 6 ng/mL for the in vitro experiment, 0.07 mg colchicine/kg/d × 14 days for the nude mouse experiment). Our results showed that colchicine caused significantly dose-dependent antiproliferative effects on both cell lines (all p < 0.0001). Nude mouse (BALB/c-nu) experiments showed that the increased tumor volume ratios in colchicine-treated mice were significantly lower than control mice started from the 11th day of treatment (p = 0.0167). The tumor growth rates in colchicine-treated mice after 14 days of treatment were significantly lower than in control mice (0.147 ± 0.004/d vs. 0.274 ± 0.003/d, p = 0.0015). In addition to the well-known direct colchicine-tubulin interaction as a common anticancer mechanism of colchicine, microarray and quantitative reverse transcriptase-polymerase chain reaction showed that the antiproliferative effects of both 2 ng/mL and 6 ng/mL colchicine on C14/KMUH cells could be partially explained by downregulations of both HSD11B2 and MT-COI. There was no effect of colchicine on MT-COI expression in C51/KMUH cells, however, 6 ng/mL colchicine also downregulated HSD11B2 in this cell line. In conclusion, clinically acceptable colchicine concentrations can inhibit the proliferation of human cholangiocarcinoma cells. This drug has good potential for the palliative treatment of cholangiocarcinoma due to its low cost and our long-standing prescription experience.
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: linzuyau@yahoo.com.tw.
authors.forename: Zu-Yau
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Kuoc
authors.affiliation: Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000818:Animals; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D003078:Colchicine / Q000627:therapeutic use*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D003576:Electron Transport Complex IV; C581860:cytochrome c oxidase subunit I, human; D003078:Colchicine
keywords: Animal study; Cholangiocarcinoma; Colchicine; Proliferation