上皮性卵巢癌中PARP-1的表达及其与EMT的关系

 目的: 探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)中聚腺苷二磷酸核糖聚合酶-1poly(ADP-ribose) polymerase-1,PARP-1]的表达及其与上皮-间质转化(epithelial-mesenchymal transition,EMT)的关系。方法: 免疫组化、实时荧光定量PCR法检测EOC和良性卵巢肿瘤组织中PARP-1、E-钙黏蛋白(E-cadherin)、波形蛋白(vimentin)和转录调控因子Snail的表达;Western blotting法检测高效PARP-1抑制剂PJ34处理SKOV3细胞后PARP-1、E-cadherin、vimentin和Snail蛋白的表达。结果: PARP-1、vimentin和Snail在EOC中阳性表达率高于良性卵巢肿瘤组织,而E-cadherin则相反,差异均有统计学显著性(P<0.05)。PARP-1、E-cadherin、vimentin和Snail与EOC的病理分级、临床分期和有无淋巴结转移有关(P<0.05),与年龄和病理类型无关。E-cadherin表达与PARP-1表达呈负相关(P<0.05),vimentin、Snail表达与PARP-1表达呈正相关(P<0.05)。EOC中PARP-1、vimentin和Snail mRNA的相对表达量高于良性卵巢肿瘤组织,E-cadherin mRNA的相对表达量低于良性卵巢肿瘤组织,差异均具有统计学显著性(P<0.05)。PJ34处理SKOV3细胞后,PARP-1、vimentin和Snail的蛋白水平明显下降,E-cadherin的蛋白水平显著提高,差异有统计学显著性(P<0.05)。结论: PARP-1通过调控E-cadherin、vimentin和Snail的表达促进EOC上皮间质转化。PARP-1及其参与的上皮-间质转化在EOC进展中发挥重要作用。

Expression of PARP-1 in epithelial ovarian cancer and its relationship with epithelial-mesenchymal transition

AIM: To investigate the expression of poly(ADP-ribose) polymerase-1(PARP-1) in the epithelial ovarian cancer(EOC) and its relationship with epithelial-mesenchymal transition(EMT). METHODS: The expression of PARP-1, E-cadherin, vimentin and Snail was detected in the EOC and benign ovarian tumor tissues by immunohistochemical method and real-time PCR. The expression of PARP-1, E-cadherin, vimentin and Snail proteins in the SKOV3 cells treated with efficient PARP-1 inhibitor PJ34 was determined by Western blotting. RESULTS: The positive expression rates of PARP-1, vimentin and Snail were significantly higher in the EOC than that in the benign ovarian tumor tissues, whereas the positive expression rate of E-cadherin was the opposite(P<0.05). The expression of PARP-1, E-cadherin, vimentin and Snail in the EOC was associated with the histological grade, clinical stage and lymphatic metastasis(P<0.05), but no relationship with age and pathological types was observed. The expression of E-cadherin in the EOC was negatively co-related to that of PARP-1. In contrast, the expression of vimentin and Snail in the EOC was positively co-related to that of PARP-1. The relative mRNA expression of PARP-1, vimentin and Snail in the EOC was significantly higher than that in the benign ovarian tumor tissues(P<0.05), while the mRNA expression of E-cadherin in the EOC was remarkably lower than that in the benign ovarian tumor tissues(P<0.05). The protein expression of PARP-1, vimentin and Snail in the SKOV3 cells was significantly decreased(P<0.05), while E-cadherin protein was increased after treated with PJ34(P<0.05). CONCLUSION: PARP-1 may contribute to the onset of EMT in the EOC by regulating the expression of E-cadherin, vimentin and Snail. The role of PARP-1, which is relevant to EMT, might be important in the development of ovarian cancer.