维生素E琥珀酸酯联合三苯氧胺对乳腺癌荷瘤裸鼠的治疗作用

Therapeutic effect of vitamin E succinate combined with tamoxifen on graft model of human breast cancer in nude mice

目的:检测维生素E琥珀酸酯(VES)联合三苯氧胺(TAM)对荷乳腺癌裸鼠的体内肿瘤的抑制作用,并探讨其可能的作用机制。方法:40只裸鼠皮下接种MCF-7乳腺癌细胞建立荷瘤裸鼠模型,分为空白对照组(不予治疗)、TAM治疗组(予5 mg/kg TAM治疗)、VES治疗组(予150 mg/kg VES治疗)、联合治疗组(5 mg/kg TAM+150 mg/kg VES),每组10只,治疗4周后测量各组肿瘤大小,流式细胞仪检测细胞周期变化和细胞表面Fas和FasL表达,免疫组化法检测肿瘤组织Fas和FasL表达,TUNEL法检测细胞凋亡指数的变化。结果:VES联合TAM对荷乳腺癌裸鼠体内肿瘤具有明显的增殖抑制作用,较单用VES或TAM抑制作用增强(P<0.05)。细胞周期分析显示,联合药物治疗后肿瘤细胞表现为明显的G0/G1期阻滞,肿瘤组织和细胞表面的Fas和FasL表达上调,同时细胞的凋亡率升高。结论:VES联合TAM对荷乳腺癌裸鼠体内肿瘤具有协同抑制作用,其机制可能与上调肿瘤细胞Fas/FasL表达,促进细胞凋亡有关。

Objective：To investigate the antitumor effect of vitamin E succinate combined with tamoxifen on the graft model of human breast cancer in nude mice and to analyze the possible mechanism. Methods： MCF-7 human breast cancer cells were inoculated subcutaneously in 40 nude mice. Then the mice were equally divided into 4 groups： blank control group （ non-treatment） ,TAM treatment group（5 mg/kg） ,VES treatment group（150 mg/kg） and the TAM＋VES treatment group（TAM 5 mg/ kg ＋VES 150 mg/kg）. The size of the tumor was measured and both the cell cycle and cell surface Fas/FasL were determined by flow cytometry 4 weeks after treatment. Fas/FasL expression in tumor tissue was detected with immunohistochemistry and cell apoptosis was detected by TUNEL method. Results： The co-administration of VES and TAM had more potent inhibitory effect on the growth of solid tumor than VES or TAM administered alone （P〈0.05）. Tumor cells in TAM＋VES group were blocked at G0/G1 phase and Fas/FasL expressions in tumor tissue and cell surface were up-regulated, accompanied with increased apoptotic rate. Conclusion： The combination of VES with TAM has syngergetic inhibitory effect on breast cancer graft in nude mice,which may be due to the up-regulation of Fas/FasL expression and the induction of apoptosis.