苯异羟肟酸衍生物抑制胃癌细胞活力的体外实验

Experimental study of benzhydroxamic acid derivative in suppressing the activity of gastric cancer cell line in vitro

目的:探讨苯异羟肟酸衍生物对胃癌细胞生长的抑制作用及其机制. 方法:以胃癌细胞株7901为靶细胞,采用体外细胞培养技术评价苯异羟肟酸衍生物E(E药物)对肿瘤细胞活性的影响,通过光学和电子显微镜对E药物作用后细胞形态学进行观察,用免疫组化和RT-PCR方法检测细胞凋亡. 结果:E药物对胃癌细胞活性有抑制作用,作用1～4 d后7901活细胞数分别下降54.55%, 82.05%, 94.85%和94.97%;作用5和6 d时没有细胞存活,各时间点的E药物组与空白对照组比较活细胞数明显下降(1 d:t=4.24, P=0.005; 2 d:t=8.99, P=0.000; 3 d:t=13.36, P=0.000; 4 d:t=17.59, P=0.000; 5 d:t=31.00, P=0.000; 6 d:t=22.52, P=0.000). 光镜及电镜观察:E药物作用后肿瘤细胞变圆,有的出现裂解和皱缩,主要以凋亡为主. E药物作用肿瘤细胞后能抑制Survivin基因表达. 结论:E药物对胃癌7901细胞有抑制增殖作用;其抑制作用与5-氟尿嘧啶(5-FU)和顺铂(DDP)作用相同或近似. 苯异羟肟酸衍生物E主要通过抑制Survivin基因的表达引起肿瘤细胞的凋亡,从而抑制肿瘤细胞的生长.

AIM： To study the inhibitory action of derivative of benzhydroxamic acid on gastric cancer cell line and the mechanism. METHODS： Benzhydroxamic acid derivative E （ medicine E） was artificially synthesized. The gastric cancer line 7901 was selected to serve as the target cell. The effect of medicine E on tumor cell activity was examined by cell culture technology in vitro. The change of morphology and the ultrastructure after treatment with medicine E was observed with the optic microscope and the electron microscope. The effect mechanism of medicine E was studied with immunohistochemistry and the PCR method. RESULTS： The gastric cancer cell activity was inhibited after treatment with medicine E. The cell number decreased to 54.55%, 82.05%, 94.85% and 94.97% after the cells were treated with medicine E for 1 d to 4 d, respectively. There was no live cells after the cells were treated with medicine E for 5 d and 6 d. The live cell number of medicine E group was significant reduced compared with that of blank control at different testing time points （ 1 d. t = 4.24, P = 0.005; 2 d： t=8.99, P=0.000; 3 d： t=13.36, P=0.000; 4 d： t=17.59, P=0.000; 5 d： t=31.00, P=0.000; 6 d： t=22.52, P=0. 000）. The tumor cellular shape changed after treatment. The survivin gene was suppressed after gastric cancer cells were treated with medicine E. CONCLUSION： The medicine E has inhibitory action on gastric cancer 7901 cells. The inhibitory action was the same or similar compared with that of 5-FU and DDP. The tumor cell apoptosis and growth suppression are caused mainly by suppression of the survivin gene expression after treatment with medicine E.