Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinorna cells
Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinorna cells
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DOI：
10.1097/00001813-200503000-00008
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发表时间：
2005-03-01
影响因子：
2.3
通讯作者：
Liao, HF
中科院分区：
文献类型：
--
作者：
Chen, YJ;Shieh, CJ;Liao, HF
去甲斑蝥素 (NCTD) 是一种潜在的抗癌药物，是从斑蝥中分离出的斑蝥素的去甲基化类似物。本研究探讨了NCTD对肿瘤侵袭和转移的影响。 NCTD 对 CT26 结直肠腺癌细胞的细胞毒性测定显示细胞活力呈剂量和时间依赖性下降。 NCTD（50μM）处理的CT26细胞不仅显示细胞侵袭被抑制65.6%，而且还降低基质金属蛋白酶-2和-9的活性。 NCTD以剂量依赖性方式降低CT26细胞的粘附能力。在浓度为100 μM时，NCTD显示多种钙粘蛋白-连环蛋白粘附分子的表达下调，包括桥粒芯糖蛋白、N-钙粘蛋白、α-和β-连环蛋白，而E-钙粘蛋白和γ-连环蛋白没有明显变化。 BALB/c小鼠腹腔注射NCTD（2mg/kg/天）既降低了CT26细胞的肺转移能力，又延长了小鼠的生存天数。这些结果表明它可以有效阻断肿瘤侵袭和转移。 (C) 2005 年利平科特·威廉姆斯·威尔金斯。
Norcantharidin (NCTD), a potential anti-cancer drug, is the demethylated analog of cantharidin isolated from blister beetles. The present study investigated the effect of NCTD on tumor invasion and metastasis. A cytotoxicity assay of NCTD in CT26 colorectal adenocarcinoma cells showed a dose- and time-dependent decrease in cell viability. NCTD (50muM)-treated CT26 cells not only showed an inhibited cell invasion of 65.6%, but also decreased the activity of matrix metalloproteinase-2 and -9. NCTD decreased the adhesive ability of CT26 cells in a dose-dependent manner. At a concentration of 100 muM, NCTD showed a down-expression of several cadherin-catenin adhesion molecules, including Desmoglein, N-cadherin, and alpha- and beta-catenin, while there were no obvious changes in E-cadherin and gamma-catenin. Intraperitoneal injection of NCTD (2 mg/kg/day) in BALB/c mice reduced both the pulmonary metastatic capacity of CT26 cells and prolonged the survival day of the mice. These results demonstrated that it was effective in blocking both tumor invasion and metastasis. (C) 2005 Lippincott Williams Wilkins.