Par-4基因增敏顺铂对肾母细胞瘤荷瘤裸鼠生长的抑制作用

Inhibitory effect on growth of xenograft with Wilms' tumor by Par-4 gene sensitizing cisplatin

目的 :探讨腺病毒介导的前列腺凋亡反应因子-4(prostate apoptosis response-4,Par-4)协同顺铂(CDDP)对人肾母细胞瘤细胞SK-NEP-1裸鼠皮下移植瘤的影响。方法:采用人肾母细胞瘤细胞株SK-NEP-1建立BALB/c裸鼠皮下移植瘤模型,分别用表达Par-4的腺病毒、CDDP及两者联合治疗,随机分成5组:Par-4+CDDP组、Par-4组、CDDP组、空Par-4(不表达Par-4的对照腺病毒)组、空白对照组。测定移植瘤的体积及瘤重,通过HE染色及免疫组化分析,检测移植瘤组织中Par-4、GRP78及BAX蛋白的表达水平。结果:Par-4+CDDP组、Par-4组及CDDP组均有抑制裸鼠移植瘤生长的作用,瘤重差异有统计学意义(P<0.05),其中,Par-4+CDDP组优于Par-4组与CDDP组。而空Par-4组与空白对照组相比,差异无统计学意义。Par-4+CDDP组能明显上调Par-4、GRP78及BAX蛋白表达(P<0.05)。结论:外源性Par-4协同CDDP抑制裸鼠移植瘤的生长可能是外源性Par-4通过结合GRP78后上调BAX蛋白所致。

Objective：To study the effects of adenovirus mediated prostate apoptosis response-4（Par-4）combined with cisplatin（CDDP）on subcutaneous xenografts of hunan Wilms＇ tumor cells SK-NEP-1 in nude mouse. Methods：Inhibition effect of subcutaneous transplanted Wilms＇ tumor model were established in BALB / c nude mice,and then the nude mice were randomly divided into five groups,namely Par-4＋CDDP group,Par-4 group,CDDP group,negative control Par-4 group and blank control group.The volumes and weights of the transplanted tumors were measured. Transplanted tumor tissues were used to detect the expression levels of Par-4,GRP78 and BAX protein by HE staining and immunohistochemical analysis. Results：The tumor growth was inhibited in Par-4＋CDDP group,Par-4 group and CDDP group,and there were differences in the tumor weight amorg 3 groups（P〈0.05）. The inhibition effect of Par-4＋CDDP group was superior to the Par-4 group and CDDP group. There was no statistically significace in tumor inhibition between blank control group and negative control Par-4 group. Par-4＋CDDP can significantly increased Par-4,GRP78 and BAX protein（P〈0.05）. Conclusion： Ectopic Par-4 in combination with CDDP suppressed the cancer-xenografted growth in nude mice,which might up-regulate BAX protein,the result of the interraction of extracellular Par-4 and GRP78.