斑蝥素抑制舌癌细胞生长及转移能力  

Cantharidin Inhibits Growth and Metastatic Ability of Tongue Cancer Cells

作　　者：郑乔丹[1] 李伟[2] 殷红[2] 

机构地区：[1]广州医科大学附属第三医院检验科,广东广州510140 [2]苏州大学附属第一医院肿瘤科,江苏苏州215006

出　　处：《中山大学学报（医学科学版）》2014年第5期650-656,共7页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(81101867);江苏省卫生厅医学科研项目(Z201206);苏州市科教兴卫青年科技项目(SWKQ1003);苏州市科技发展计划项目(SYSD2012137;SYSD201335)

摘　　要：【目的】观察斑蝥素(Cantharidin)对舌癌细胞株Tca8113、CAL-27生长及转移能力的抑制作用。【方法】舌癌细胞株Tca8113、CAL-27处理组采用斑蝥素处理,通过噻唑蓝(MTT)比色法检测细胞生长能力;通过流式细胞术检测细胞的细胞周期分布;通过实时定量PCR和Western-blot检测p21、细胞周期蛋白依赖激酶1(CDK1)、基质金属蛋白酶-2、9(MMP-2,9)基因表达的变化;通过Transwell小室及划痕实验检测斑蝥素对细胞侵袭和迁移能力的影响。【结果】斑蝥素抑制舌癌细胞生长,呈剂量和时间依赖性(P﹤0.01)。斑蝥素处理后G2/M期细胞比例上升(P﹤0.01),呈G2/M期阻滞。斑蝥素处理后,抑制G2/M周期转换的p21表达上调(P﹤0.01),而促进G2/M周期转换的CDK1表达下调(P﹤0.01)。斑蝥素可显著抑制舌癌细胞的侵袭能力,处理24 h使Tca8113、CAL-27细胞侵袭力分别下降(93.50±3.32)%(P﹤0.01),(61.33±4.11)%(P﹤0.01)。斑蝥素处理后MMP-2、9 mRNA表达量显著降低。划痕实验显示斑蝥素可显著抑制舌癌细胞的迁移能力(P﹤0.01),处理12 h使Tca8113、CAL-27细胞迁移能力分别下降(57.60±8.98)%(P﹤0.01),(49.94±5.63)%(P﹤0.01)。【结论】斑蝥素通过阻滞细胞周期抑制舌癌细胞的生长,并通过抑制舌癌细胞迁移和对基质的降解,抑制舌癌细胞转移。[Objective] To investigate the effects of cantharidin on the growth and metastatic ability of tongue cancer cell lines Tca8113 and CAL-27.[Methods] Cell proliferation was measured by methylthiazol tetrazolium （MTT） assay.Cell cycle was tested by flow cytometry.The expressions of p21,CDK1 （Cyclin dependent kinase 1）,matrix metalloproteinase-2,9 （MMP-2,9） were detected by real-time PCR and Western blot analysis.Invasion ability was assessed by Transwell invasion assay.Migration ability was evaluated by wound healing assay.[Results] Cantharidin inhibited tongue cancer cell growth in a concentration and time-dependent manner （P ＜ 0.01）.After treatment with cantharidin,the ratio of G2/M cells was significantly increased （P ＜ 0.01）.Real-time PCR showed that expression of p21,which represses the G2/M cell cycle transition,was up-regulated （P ＜ 0.01）,while CDK1,which promotes the G2/M cell cycle transition,was down-regulated （P ＜ 0.01）.Treatment with cantharidin for 24 h repressed the invasion ability of Tca8113 and CAL-27 cells by （93.50±3.32） ％ （P ＜ 0.01） and （61.33±4.11）％ （P ＜ 0.01）,respectively.After cantharidin treatment,the expression of MMP-2,9 were significantly reduced.Wound healing assay proved that cantharidin repressed the migration of tongue cancer cells by （57.60±8.98） ％ （P ＜ 0.01） and （49.94±5.63） ％,（P ＜ 0.01） in Tca8113 and CAL-27 cells respectively.[Conclusion] Cantharidin can significantly inhibited the growth of tongue cancer cells through G2/M cell cycle arrest and inhibited the metastatic ability of tongue cancer cells through repressing on the migration and degradation of matrix.

关 键 词：斑蝥素 舌癌 生长 转移 

分 类 号：R33[医药卫生—人体生理学]