摘要目的 探讨蛋白亲环素D(CypD)与肾透明细胞癌(ccRCC)的发生、发展的关系,同时探讨CypD在索拉非尼治疗ccRCC中的作用及机制.方法 取人ccRCC标本53例和癌旁组织标本34例,应用免疫组织化学法比较其CypD蛋白表达差异;采用反转录-聚合酶链反应(RT-PCR)及Western blot法比较人正常肾小管上皮细胞株HK-2、人肾癌细胞株A498、人ccRCC细胞株786-O中mRNA和蛋白表达的差异;用索拉非尼作用于786-O细胞株,观察索拉非尼对CypD基因表达的影响.结果 在癌旁组织标本中CypD免疫反应评分为(7.1±0.2)分,显著高于ccRCC标本评分[(1.6±0.4)分,P ＜0.01];A498及786-O细胞株中mRNA和蛋白表达较HK-2细胞株分别下降了75％和69％ (mRNA);77％和65％(蛋白),差异有统计学意义(P＜0.01);50 μmol/L索拉非尼24h能上调786-O细胞株中CypD基因蛋白的表达的63％.结论 CypD与ccRCC的发生、发展呈负相关.

abstractsObjective To investigate the relationship between Cyclophilin D (CypD) and occurrence and development of clear cell-renal cell carcinoma (ccRCC),and explore the action mechanism of CypD in the treatment of cRCC with sorafenib.Methods We used immunohistochemical analysis to compare CypD expression in human ccRCC tissues (n =53) and adjacent non-cancerous tissues (ANCT,n =34),and the mRNA and protein expression differences in HK-2,A498 and 786-O cell lines were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting respectively.The protein expression of CypD was observed in 786-O cell line treated with sorafenib.Results According to the CypD immunoreactive intensity,the immunoreactivity score of CypD in the ANCT samples was 7.1 ±0.2,which was significantly higher than that of the ccRCC samples (1.6 ±0.4,P ＜0.01).As ompared with HK-2 cells,the expression of CypD mRNA and protein was significantly downregulated in 786-O and A498 cells [75％ and 69％ (mRNA);77％ and 65％ (protein),P ＜ 0.01].The CypD protein expression in 786-O cells treated with sorafenib (50 μmol/L) for 24 h was increased by 63％.Conclusion CypD is negatively correlated with the occurrence and development of ccRCC.