去甲基斑蝥素抑制大腸腺癌細胞侵犯與轉移之能力

Inhibitory Effect of Norcantharidin on Tumor Invasion and Metastasis in Colorectal Adenocarcinoma Cells

廖慧芬(Hui-Fen Liao) ； 張偉民(Wei-Min Chang) ； 郭正典(Cheng-Deng Kuo)

《中西整合醫學雜誌》 7卷1期 (2005/12) Pp. 11-19

https://doi.org/10.29613/JICWM.200512.0002

摘要

去甲基斑蝥素（norcantharidin，簡稱NCTD）是一種有發展潛力之抗癌藥物，其結構源自去除甲基修飾的班蝥素(cantharidin)。本研究主要探討NCTD對於腫瘤細胞的侵犯(invasion)與轉移(metastasis)之抑制能力。NCTD對於減少CT26大腸腺癌細胞之存活率表現出濃度跟時間的依存關係。以50μM的NCTD處理CT26細胞24小時後，NCTD不僅顯現出高達65.6%的抑制細胞侵犯力，同時也降低了基質金屬結合蛋白酵素(matrix metalloproteinases, MMP)-2與－9的活性。此外，NCTD亦降低了CT26細胞之黏附(adhesion)能力。當NCTD濃度達到100μM時，可降低Cadherin-Catenin這一群細胞黏附因子(adhesion molecules)的表現，其中包含：Desmoglein、N-cadherin、α-及β-catenin。然而，NCTD對於E-cadherin和γ-catenin的表現，則並未有顯著的改變。動物實驗中，我們也建立CT26大腸腺癌細胞之肺轉移模式，首先將CT26細胞透過尾靜脈注射入BALB/c小鼠中，再利用腹腔注射NCTD，以每日2 mg/kg/day之劑量。結果顯示，NCTD能有效地降低CT26細胞之肺轉移現象，同時可延長小鼠的存活天數。因此，本研究證明了去甲基斑蝥素能有效地阻止腫瘤細胞的侵犯及轉移之能力。

關鍵字

去甲基斑蝥素NCTD ； 大腸腺癌 ； 腫瘤侵犯 ； 肺轉移

並列摘要

Norcantharidin (NCTD) is a potential anti-cancer drug derived by demethylation from traditional medicine Cantharidin that was isolated from the Blister beetles. This study investigated the effect of NCTD on the tumor invasion and metastasis of colorectal adenocarcinoma. The cytotoxicity of NCTD in CT26 colorectal adenocarcinoma cells showed a dose-and time-dependent decrease in cell viability. CT26 cells treated by 50 μM NCTD not only inhibited cell invasion by 65.6%, but also decreased the activity of matrix metalloproteinase (MMP)-2 and 9. NCTD also decreased the adhesive ability of CT26 cells in a dose-dependent manner. At a concentration of 100 μM, NCTD down-regulated the expression of several cadherin-catenin adhesion molecules, including desmoglein, N-cadherin, α-and β-catenin, whereas no obvious changes in E-cadherin and γ-catenin were observed. In animal model, intraperitoneal injection of NCTD (2 mg/kg/day) in BALB/c mice reduced the pulmonary metastatic capacity of CT26 cells and prolonged the survival day of the mice. These results suggested that NCTD might be effective in blocking both tumor invasion and metastasis of colorectal adenocarcinoma.

並列關鍵字

norcantharidin NCTD ； colorectal adenocarcinoma ； tumor invasion ； pulmonary metastasis