增免抑瘤颗粒剂对卵巢癌荷瘤小鼠肿瘤生长及细胞凋亡的影响

Effects of "Zengmian Yiliu Granule" on ovarian carcinoma xenograft and cell apoptosis in ovarian carcinoma-bearing mice

目的研究增免抑瘤颗粒剂(ZMYL)对卵巢癌皮下移植瘤的抑制作用,并从细胞凋亡途径探讨其作用机制。方法建立卵巢癌荷瘤小鼠模型,随机分为5组:对照组、紫杉醇组、ZMYL高、中、低剂量组,每组8只。给予相应干预措施。给药10天后处死荷瘤小鼠,称取瘤重计算抑瘤率,电镜观察瘤组织超微结构,TUNEL法检测凋亡指数,实时荧光定量PCR法检测细胞凋亡促进及抑制因子Bax、Bcl-2 mRNA表达。结果①紫杉醇及ZMYL各组均能抑制移植瘤增殖,ZMYL高、中、低剂量组的抑瘤率分别为34.64%、31.60%、30.03%。②病理检查ZMYL各组与紫杉醇组肿瘤细胞均有典型凋亡形态学改变。③与对照组比较,紫杉醇组及ZMYL高、中、低剂量组有诱导肿瘤细胞凋亡作用,差异有统计学意义(P<0.05)。④与对照组比较,紫杉醇组及ZMYL高、中剂量组能上调移植瘤内Bax mRNA表达和下调移植瘤内Bcl-2 mRNA表达,差异有统计学意义(P<0.05)。其中ZMYL高剂量组上调Bax及下调Bcl-2表达的作用强于ZMYL中剂量组,差异有统计学意义(P<0.05);ZMYL中剂量组上调Bax以及下调Bcl-2表达的作用强于ZMYL低剂量组,差异有统计学意义(P<0.05)。结论 ZMYL颗粒剂具有一定的抑制卵巢癌细胞增殖的作用,其机制与上调Bax、下调Bcl-2 mRNA表达、促进肿瘤细胞凋亡有关。

Objective To investigate the inhibitory effect of ＂Zengmian Yiliu Granule＂ on ovarian carcinoma xenograft from the viewpoint of cell apoptosis.Methods The transplanted tumor models with human ovarian carcinoma were established.The tumor-bearing mice were randomly divided into five groups： control group,paclitaxel group,＂Zengmian Yiliu Granule＂（ZMYL） of high-,medium-and low-dose group.Each group included eight mice and was treated for ten days.The tumor-inhibiting effect and cell apoptosis on ovarian carcinoma xenograf was analyzed by the calculation of the tumor weight and inhibitory rate,ultrastructure of tumor by electronic microscope,apoptotic index by TUNEL,and the expressions of apoptosis promotion and inhibition factors Bax and Bcl-2 mRNA by RT-PCR.Results ①The paclitaxel and ZMYL could inhibit the proliferation of ovarian carcinoma xenograft,and the inhibitory rate of ZMYL of high-,medium-and low-dose groups were 34.64%,31.60% and 30.03% respectively.②Pathological examination showed that the tumor cells presented with typical morphological changes of apoptosis both in the each dose of ZMYL group and in the paclitaxel group.③The paclitaxel and ZMYL could induce the apoptosis of tumor cells,with significant differences of apoptotic index between these groups and the control group.④The paclitaxel and ZMYL could up-regulate the expression of Bax mRNA in the xenografts.The expression of Bax mRNA in the paclitaxel group and in the ZMYL of high-dose group had significant differences compared with the control group（P0.01）;the expression of Bax mRNA in the ZMYL of medium-dose group had a statistical difference compared with control group（P0.05）.⑤The paclitaxel and ZMYL of high-and medium-dose group could down-regulate the expression of Bcl-2 mRNA in the xenografts,with significant differences in comparison with the control group（P0.01）.Conclusion ZMYL have a certain inhibitory effect on ovarian carcinoma xenograft possibly by up-regulating the expression of Bax mRNA and down-regulating the expression of Bcl-2 mRNA to promote the apoptosis of tumor cells.