Lin Zu-Yau, Kuo Chao-Hung, Wu Deng-Chyang, Chuang Wan-Long
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.
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.
Kaohsiung J Med Sci. 2016 Feb;32(2):68-73. doi: 10.1016/j.kjms.2015.12.006. Epub 2016 Feb 2.
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.
秋水仙碱是一种非常廉价的微管解聚剂。由于微管是抗癌药物的理想靶点，本研究的目的是探讨临床上可接受的秋水仙碱浓度是否对胃癌细胞具有抗癌作用及其可能的抗癌机制。使用临床上可接受的秋水仙碱浓度（体外试验为2 ng/mL和6 ng/mL，体内试验为0.07 mg秋水仙碱/千克/天），通过增殖试验、微阵列、定量逆转录聚合酶链反应以及裸鼠研究，对两种人胃癌细胞系（即AGS和NCI-N87）进行了研究。我们的结果表明，秋水仙碱对两种细胞系的增殖具有相同的抑制作用。秋水仙碱对两种细胞系的抗增殖作用仅在浓度为6 ng/mL时才能实现（p < 0.0001）。与2 ng/mL秋水仙碱相比，在两种细胞系中，6 ng/mL秋水仙碱可使18个基因持续上调，10个基因持续下调。在这些基因中，只有上调的双特异性磷酸酶1（DUSP1）基因可能有助于秋水仙碱对胃癌细胞的抗增殖作用。裸鼠（BALB/c-nu）实验表明，治疗14天后，接受秋水仙碱治疗的小鼠的肿瘤体积增加率（p = 0.0199）和肿瘤生长速率（p = 0.024）均低于对照小鼠。总之，秋水仙碱具有用于胃癌姑息治疗的潜力。然而，只有在临床上可接受的高秋水仙碱浓度下才能实现抗癌作用。如果将该药物用于胃癌的姑息治疗，必须监测秋水仙碱的血浆浓度。
