二烯丙基二硫对裸鼠体内人结肠癌细胞增殖的影响

背景与目的:二烯丙基二硫(diallyl disulfide,DADS)在体外可抑制多种肿瘤细胞增殖,但在体内抗肿瘤作用的研究报道较少.本实验旨在研究DADS对裸鼠体内人结肠癌SW480细胞增殖的影响.方法:建立人结肠癌裸鼠移植瘤模型,实验动物分为DADS组及对照组.观察DADS作用后移植瘤体积和重量的变化,通过光镜和电镜观察移植瘤细胞形态学变化,通过免疫组织化学和形态定量图像分析系统检测瘤组织内增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)蛋白表达变化,用流式细胞术检测移植瘤细胞周期分布.结果:DADS在体内能明显抑制移植瘤的生长,相对肿瘤增殖率为49.85%;组织学分析显示DADS组瘤细胞异型性降低,核质比下降,胞浆内细胞器丰富,部分胞核呈退行性变,可见凋亡小体;免疫组化示两组移植瘤组织PCNA蛋白均有阳性表达,DADS组(149.02±4.26)与对照组(178.86±7.69)比较,裸鼠移植瘤组织内PCNA蛋白表达明显减弱(P＜0.05);流式细胞术分析显示,对照组移植瘤细胞中G2/M期细胞为18.8%,与对照组比较,DADS组G2/M期细胞(38.6%)显著增多.结论:DADS可体内抑制人结肠癌SW480细胞增殖,使癌细胞阻滞于G2/M期.

Inhibitory effect of diallyl disulfide on proliferation of human colon cancer cell line SW480 in nude mice

BACKGROUND & OBJECTIVE: Diallyl disulfide (DADS) can inhibit the proliferation of various cancer cell lines in vitro, but little is known about its in vivo antitumor effect. This study was to investigate the inhibitory effect of DADS on the proliferation of human colon cancer cell line SW480 in nude mice. METHODS: After subcutaneous transplantation of SW480 cells in the back of nude mice, 5 mice received intraperitoneal injection of DADS (30 mg/kg), and 5 received intraperitoneal injection of normal saline as control. The body weight of nude mice and tumor growth were measured. The morphology of tumor was observed under optical microscope and electron microscope. The expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry and morphometric quantitative analysis. Cell cycle distribution was analyzed by flow cytometry (FCM). RESULTS: The growth of transplanted tumor was inhibited markedly by DADS; the relative tumor growth rate (T/C%) was 49.85%. In DADS group, the cellular atypia and nucleus-cytoplasm ratio were decreased, intracytoplasm cellular organs were abundant, and retrograde alters and apoptotic bodies were manifested in some cells. The protein level of PCNA was significantly lower in DADS group than in control group (149.02+/-4.26 vs. 178.86+/-7.69, P<0.05). SW480 cells in DADS group were arrested in G2/M phase; the G2/M phase proportion was significantly higher in DADS group than in control group (38.6% vs. 18.8%, P<0.01). CONCLUSION: DADS has significant inhibitory effect on the proliferation of human colon cancer SW480 cells in nude mice and can arrest cell cycle in G2/M phase.