秦皮乙素对小鼠皮下Hepa1-6肝癌移植瘤凋亡基因Bcl-2、Bax表达的影响

Effects of Aesculetin on the Expression of Bcl-2 and Bax in Mice with Hepatoma Subcutaneous Transplantable Tumor Hepa1-6

目的:研究秦皮乙素对小鼠皮下Hepa1-6肝癌移植瘤凋亡基因-2(Bcl-2)、Bcl-2相关X蛋白(Bax)表达的影响。方法:40只C57BL/6J小鼠右腋皮下接种Hepa1-6肿瘤细胞,复制小鼠肝癌皮下移植瘤模型。实验分为5组,即模型(生理盐水)、环磷酰胺和秦皮乙素高、中、低剂量(700、400、200mg·kg-1)组。复制模型后第3天开始腹腔注射给药,15d后处死小鼠取出瘤组织,称瘤重,计算抑瘤率。RT-PCR检测凋亡基因Bcl-2mRNA、BaxmRNA的表达,Westernblot法检测Bcl-2蛋白、Bax蛋白表达。结果:秦皮乙素高、中、低剂量组抑瘤率分别为55.42%、40.37%、20.33%,与模型组比较有显著性差异(P<0.01);秦皮乙素高、中、低剂量组BaxmRNA和Bax蛋白的表达均显著高于模型组(P<0.01),Bcl-2mRNA和Bcl蛋白的表达均显著低于模型组(P<0.01)。结论:秦皮乙素对小鼠Hepa1-6肝癌瘤生长起到一定的抑制作用,其机制可能与通过上调Bax、下调Bcl-2基因的表达有关。

OBJECTIVE：To study the effects of aesculetin on the expression of Bcl-2 and Bcl-2 proteins（Bax）in mice with hepatoma subcutaneous transplantable tumor Hepa1-6.METHODS：40 C57BL/6J mice underwent right axillary subcutaneous vaccination of Hepa1-6 hepato-carcinoma cells to induce hepatoma subcutaneous transplantable tumor model.The experimental rats were divided into 5 groups,i.e.model group（normal saline）,cyclophosphamide（CTX）group,aesculetin high-dose,medium-dose and low-dose groups（700,400,200 mg·kg-1）.On the third day after modeling,model mice were given drug intravenously.The mice were killed after 15 days.The tumor tissues separated and weighted and inhibition rate was calculated.The mRNA expression of Bcl-2 and Bax was detected by RT-PCR assay,and the protein expression of Bcl-2 and Bax was Western blot.RESULTS：The tumor-inhibition rates of aesculetin high-dose,medium-dose and low-dose groups were 55.42%,40.37% and 20.33%.There was significant difference between aesculetin groups and model group（P0.01）.The mRNA expression and protein expression of Bax in aesculetin groups were all higher than model group（P0.01）;while mRNA expression and protein expression of Bcl-2 were lower than model group（P0.01）.CONCLUSION：Aesculetin could inhibit the growth of Hepa1-6 hepatoma.Its mechanism is probably associated with the expression up-regulation of Bax and the expression down-regulation of Bcl-2.