title: Anticancer effects of clinically acceptable colchicine concentrations on human gastric cancer cell lines.
abstract: Colchicine is a very cheap microtubule destabilizer. Because microtubules are an ideal target for anticancer drugs, the purpose of this study was to investigate whether clinically acceptable colchicine concentrations have anticancer effects on gastric cancer cells, and its possible anticancer mechanisms. Two human gastric cancer cell lines (i.e., AGS and NCI-N87) were investigated by proliferative assay, microarray, quantitative reverse transcriptase-polymerase chain reaction, and a nude mice study using clinically acceptable colchicine concentrations (2 ng/mL and 6 ng/mL for in vitro tests and 0.07 mg colchicine/kg/d for in vivo tests). Our results showed that colchicine had the same inhibitory effects on the proliferation of both cell lines. The antiproliferative effects of colchicine on both cell lines were achieved only at the concentration of 6 ng/mL (p < 0.0001). In both cell lines, 18 genes were consistently upregulated and 10 genes were consistently downregulated by 6 ng/mL colchicine, compared with 2 ng/mL colchicine. Among these genes, only the upregulated DUSP1 gene may contribute to the antiproliferative effects of colchicine on gastric cancer cells. The nude mice (BALB/c-nu) experiment showed that colchicine-treated mice after 14 days of treatment had lower increased tumor volume ratios (p = 0.0199) and tumor growth rates (p = 0.024) than the control mice. In conclusion, colchicine has potential for the palliative treatment of gastric cancer. However, the anticancer effects are achieved only at high clinically acceptable colchicine concentrations. Monitoring the colchicine plasma concentration is mandatory if this drug is applied for the palliative treatment of gastric cancer.
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: Kuo
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
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.
authors.forename: Wan-Long
authors.initials: WL
authors.lastname: Chuang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050257:Tubulin Modulators; D003078:Colchicine
keywords: Animal study; Colchicine; Gastric cancer; Proliferation