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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 investigate the effect of adenovirus-mediated prostatic apoptosis response factor-4 (PAR-4) and cisplatin (CDDP) on human neoplastic cell line SK-NEP-1 in nude mice influences. METHODS: BALB / c nude mice model of subcutaneous xenograft was established by using human nephroblastoma cell line SK-NEP-1 and divided into 5 groups randomly with Par-4 expressing adenovirus, CDDP and their combination therapy: Par- 4 + CDDP group, Par-4 group, CDDP group, empty Par-4 (control adenovirus not expressing Par-4) group, and blank control group. The tumor volume and tumor weight were measured. The expression of Par-4, GRP78 and BAX protein in tumor tissue were detected by HE staining and immunohistochemistry. Results: Par-4 + CDDP group, Par-4 group and CDDP group all inhibited the growth of xenografted tumor in nude mice, the difference was statistically significant (P <0.05) Par-4 and CDDP groups. However, there was no significant difference between the null Par-4 group and the blank control group. Par-4 + CDDP group could significantly upregulate the protein expression of Par-4, GRP78 and BAX (P <0.05). CONCLUSION: Exogenous Par-4 combined with CDDP may inhibit the growth of xenografted tumors in nude mice. Par-4 may be induced by upregulation of BAX protein after GRP78 binding.