抗癌活性肽对荷人胃癌裸鼠细胞凋亡及Bcl-2、Bax表达的影响

THE EFFECTS OF ANTI-CANCER BIOACTIVE PEPTIDE ON INDUCED APOPTOSIS AND EXPRESSION OF BCL-2 AND BAX IN HUMAN GASTRIC CARCINOMA IN NUDE MICE

目的:研究抗癌活性肽(anti-cancer bioactive peptide,ACBP)对荷人胃癌裸鼠的生长和抑癌作用,探讨其诱导细胞凋亡及相关基因Bcl-2、Bax的表达及其临床意义。方法:采用透射电镜、流式细胞术(flow cy-tometry,FCM)和琼脂糖凝胶电泳方法,观察和检测肿瘤细胞的凋亡及其相关基因Bcl-2、Bax的表达。在裸鼠皮下建立人胃癌模型,将30只裸鼠随机分为对照组、ACBP组和CTX组。结果:对照组、ACBP组、CTX组的肿瘤重分别为0.52±0.12g、0.23±0.03g和0.12±0.01g,与对照组相比,后两组体重抑瘤率分别为48.08%和76.92%,ACBP组、CTX组的胃癌生长受到明显抑制,差异有显著性(P<0.01);凋亡指数(apoptotic index,AI)分别为4.05%、13.75%和7.09%,以ACBP组极为显著(P<0.01),且ACBP组裸鼠的体重、饮食及活动状态均高于CTX组和对照组。Bcl-2在对照组表达最高,ACBP组最低;Bax正好相反,后者最高,前者最低。琼脂糖凝胶电泳在ACBP组和CTX组出现明显的DNA"梯形"条带;流式细胞仪直方图显示ACBP组和CTX组呈现明显的亚二倍凋亡峰;透射电镜可见典型的凋亡小体,对照组未见有明显的凋亡小体存在。结论:ACBP对胃癌有明显的抑癌作用和诱导胃癌细胞凋亡的功能,能显著提高荷瘤体的生存质量。

Objective：To study the effects of anti-cancer bioactive peptide（ACBP） on the growth and inhibition of human gastric carcinoma in nude mice and to investigate the clinical significance of its induced apoptosis and expression of Bcl-2,Bax.Methods：The effects of inhibitor ACBP on human gastric cancer and its induced apoptosis and the expression of Bcl-2,Bax in human gastric carcinoma cells were observed with transmission electron microscope,agarose gel electrophoresis and flow cytometry.Model simulating human gastric cancer was established.Mice were randomly divided into control group,ACBP group and cytoxan（CTX） group.Results：The growth of the tumor was significantly reduced in weight of 0.52±0.12g、0.23±0.03g and 0.12±0.01g in the groups treated respectively with saline solution,ACBP and CTX and by weight inhibitory rate of 48.08% and 76.92%（P〈0.01）,compared with the control group.The AI also increased significantly in the treated mice（4.05%,13.75%,7.09%）,and AI of the ACBP group increased most significantly（P〈0.01）.The expression of Bax also increased significantly but Bcl-2 decreased in the groups treated respectively with saline solution,ACBP and CTX.Internucleosomal DNA fragments displayed the characteristic ladder-lane on electrophoresis in ACBP and CTX group.There were significantly apoptotic peak on the flow cytometer＇s graphs in the ACBP group and CTX group.Apoptotic bodies were also observed with transmiss electron microscope in the ACBP and CTX group.Conclusion：ACBP could induce apoptosis in gastric cancer cells by regulating the expression of Bcl-2 and Bax and has strong inhibitory effect on tumor growth of human gastric cancer in nude mice,and it can improve the life-quality of human gastric cancer in nude mice significantly.