Wu Chun-Chieh, Lin Zu-Yau, Kuoc Chao-Hung, Chuang Wan-Long
Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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.
Kaohsiung J Med Sci. 2015 May;31(5):229-34. doi: 10.1016/j.kjms.2015.01.008. Epub 2015 Mar 10.
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.
微管因其在有丝分裂中的关键作用而成为抗癌药物的理想靶点。秋水仙碱是一种微管解聚剂。本研究旨在探讨临床上可接受的秋水仙碱浓度对人胆管癌细胞是否具有抗癌作用。使用临床上可接受的血浆秋水仙碱浓度（体外实验为2 ng/mL和6 ng/mL，裸鼠实验为0.07 mg秋水仙碱/千克/天×14天）对两种人胆管癌细胞系（C14/KMUH、C51/KMUH）进行研究。我们的结果表明，秋水仙碱对两种细胞系均产生显著的剂量依赖性抗增殖作用（所有p < 0.0001）。裸鼠（BALB/c-nu）实验表明，从治疗第11天起，秋水仙碱治疗组小鼠的肿瘤体积增加率显著低于对照组小鼠（p = 0.0167）。治疗14天后，秋水仙碱治疗组小鼠的肿瘤生长速率显著低于对照组小鼠（0.147±0.004/天 vs. 0.274±0.003/天，p = 0.0015）。除了众所周知的秋水仙碱与微管蛋白直接相互作用作为秋水仙碱常见的抗癌机制外，基因芯片和定量逆转录聚合酶链反应显示，2 ng/mL和6 ng/mL秋水仙碱对C14/KMUH细胞的抗增殖作用可部分归因于HSD11B2和MT-COI的下调。秋水仙碱对C51/KMUH细胞中MT-COI的表达没有影响，然而，6 ng/mL秋水仙碱也下调了该细胞系中的HSD11B2。总之，临床上可接受的秋水仙碱浓度可抑制人胆管癌细胞的增殖。由于其成本低且有长期的处方经验，该药物在胆管癌的姑息治疗方面具有良好的潜力。
