摘要
目的探讨顺铂(DDP)联合长春瑞滨(VNR)对移植性肝癌的抑制作用以及可能的分子机制。方法建立H22肝癌细胞系小鼠移植瘤模型40只,随机分为对照组、顺铂组、长春瑞滨组和顺铂+长春瑞滨组,治疗结束后第2周观察肿瘤体积变化和抑瘤率,采用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL法)检测治疗后小鼠移植性肝癌肿瘤细胞凋亡率,应用免疫组化(S-P法)检测血管内皮生长因子(VEGF)、caspase-3、低氧诱导因子(HIF-Iα)表达及微血管密度(MVD)。结果治疗组小鼠皮下移植瘤体积和抑瘤率与对照组相比均具有统计学意义(P<0.05);DDP与VNR联合用药组与单独应用DDP或VNR相比均具有统计学意义(P<0.05)。TUNEL法检测显示DDP与VNR联合用药可明显诱导肝癌细胞凋亡,与各单独用药治疗组和对照组比较均具有显著差异(P<0.05)。DDP与VNR联合用药上调caspase-3,下调VEGF、HIF-Iα蛋白表达,减低MVD,与对照组比较均具有显著差异(P<0.05)。结论DDP联合VNR可明显诱导肝癌细胞凋亡发生和抑制肿瘤细胞血管化,较单独应用DDP或VNR能更有效地抑制肝癌的生长,提示DDP联合VNR在肝癌治疗中可能起到重要作用。
Objective To investigate the inhibiting efficacy of combining diamminedichloroplatinum （DDP） and vinorelbine（VNR） on implanted hepatocellular carcinoma and explore its potential mecha- nism. Methods Fourty models of implanted hepatocellular carcinoma were constructed by H22 cell lines in mice firstly and were randomly divided into 4 groups including control group,DDP group,VNR group,and DDP ＋ VNR group. The tumor volume and inhibition rate were observed in the second week after treatment. The induction of cell apoptosis was analyzed with terminal deoxynucleotidy transferase nick end labeling （TUNEL） and the expression of caspase-3, VEGF, HIF-1α and the microvascular density were detected by immunohistochemistry （S-P, streptavidin-perosidase）. Results DDP group, VNR group, and DDP ＋ VNR had smaller tumor volume and higher tumor inhibition rate （P 〈0. 05） compared with control group, respectively and combinational therapy was more effective than either DDP or VNR strategy （P 〈 0.05）. The apoptotic index for tumors injected with DDP ＋ VNR was significantly different from those injected with DDP, VNR and control group （P 〈0.05）. caspase-3 was significantly up-regulated, whereas VEGF and MVD were down-regulated （P 〈 0. 05 ） in DDP ＋ VNR group compared to control group, DDP group and VNR group （P 〈 0.05 ）. Conclusion Combination of DDP and VNR can induce cellular apoptosis and inhibit the vascularization of HCC and the growth of hepatocellular car cinoma more effectively than either DDP or VNR, which indicate that combinational therapy may play an active role in the treatment of HCC.
出处
《哈尔滨医科大学学报》
CAS
北大核心
2009年第6期539-543,共5页
Journal of Harbin Medical University
关键词
H22肝癌细胞系
凋亡
血管密度
顺铂
长春瑞滨
H22 cell line
apoptosis
vessel density
diamminedichloroplatinum
venorelbine
