齐墩果酸对H22荷瘤小鼠肿瘤组织中细胞凋亡相关蛋白表达的影响

目的:通过研究齐墩果酸在H22荷瘤小鼠肿瘤组织中细胞凋亡相关蛋白的表达的影响,探讨其在肿瘤发生、发展过程中的可能作用及意义。方法:建立H22荷瘤小鼠实体瘤模型进行体内试验,将50只已接种H22细胞株的小鼠随机分为模型组,环磷酰胺40 mg·kg-1组,齐墩果酸低、中、高剂量组(1.25,2.50,5.00 mg·kg-1),连续灌胃给药10 d;处死小鼠,检测肝/体比及脾脏指数;采用免疫组化法检测瘤体内凋亡抑制基因生存素(survivin)及B细胞淋巴瘤/白血病-2(Bcl-2)的蛋白表达水平;利用原位末端标记法检测凋亡指数。结果:齐墩果酸可改善H22荷瘤小鼠的肝/体比和脾指数,齐墩果酸低、中、高剂量组对H22荷瘤小鼠肿瘤组织中survivin蛋白表达水平比模型组均显著降低(P0.01);齐墩果酸高、中剂量组对H22荷瘤小鼠肿瘤组织中Bcl-2蛋白表达水平与模型组比较显著降低(P0.01,P0.05);细胞经齐墩果酸处理后,survivin,Bcl-2表达下调,齐墩果酸各组细胞凋亡指数与模型组比较均显著升高,差异显著(P0.01)。结论:齐墩果酸可通过抑制H22荷瘤小鼠肿瘤细胞中survivin及Bcl-2蛋白的表达,提高凋亡率,诱导肿瘤细胞凋亡,还可改善荷瘤小鼠机体免疫力。survivin,Bcl-2异常表达与肿瘤的发生密切相关,通过共同调节凋亡而发挥抗肿瘤作用。

Impact of Oleanolic Acid on Apoptosis-related Protein Expression in Mice Bearing H22 Tumor Tissue

Objective: To study effect of oleanolic acid on apoptosis related proteins expression in H22 mice tumor. Method: Mice H22 tumor-burdened tumor model was used in vivo 50 mice inoculated H22 cell lines were randomly divided into model group, cyclophosphamide group, oleanolic acid low, medium and high dose groups(1.25, 2.50, 5.00 mg · kg^-1). The detection of liver, body weight ratio and spleen index was performed. Immunohistochemical method was used to detect the expression of survivin and B cell lymphoma/leukemia-2 (Bcl-2) protein, in situ end labeling method was used to detect apoptosis index, and analyzes its relevance. Result: Oleanolic acid could improve H22 tumor-burdened mice liver and body ratio and spleen index,the survivin protein expression was significantly lower than that in the model group(P<0.01);oleanolic acid high dose group decreased significantly Bcl-2 protein expression compared with model group(P<0.01);apoptosis index was significantly increased compared with model group (P<0.01). Conclusion: Oleanolic acid can inhibit H22 mice tumor-burdened tumor cells, increase the rate of apoptosis, thus promotes apoptosis. Survivin and Bcl-2 abnormal expression is closely related to the occurrence of tumor, play a role of anti-tumor by regulating apoptosis together.