PDCD5通过Wnt/β-catenin通路抑制肾细胞癌侵袭转移及其机制研究

Inhibitory effect of PDCD5 on invasion and metastasis of renal cell carcinoma through Wnt/β-catenin pathway and its underlying mechanisms

目的探讨肾细胞癌(RCC)患者PDCD5的表达水平及其参与调控RCC侵袭与转移的可能机制。方法利用免疫组化检测RCC标本与癌旁组织中PDCD5的蛋白表达水平,同时分析PDCD5与疾病分期、预后的相关性;利用transwell及划痕实验检测PDCD5对肾癌细胞系A498侵袭与转移的影响;利用Western blot检测A498细胞转染PDCD5后MMP2、MMP9、E-cadherin、N-cadherin及Wnt/β-catenin通路的变化。结果 (1)与癌旁组织相比,RCC标本中PDCD5明显下调(P<0.001),且与疾病分期及预后正相关;(2)PDCD5明显抑制了肾癌细胞系A498的转移与侵袭能力(P<0.01);(3)PDCD5通过抑制A498细胞系中MMP2、MMP9及N-cadherin的表达水平,增强E-cadherin的表达水平调控EMT转化,同时Wnt/β-catenin通路关键蛋白下调。结论 PDCD5通过调控Wnt/β-catenin通路影响肾细胞癌EMT转化,负性调控了RCC病人的侵袭与转移进程。

Objective To investigate the expression of PDCD5 levels in patients with renal cell carcinoma（RCC） and its possible mechanisms of invasion and metastasis. Methods The expression levels of PDCD5 in RCC patient and adjacent tissues were detected by immunohistochemistry. The relationship between PDCD5 and disease stage or prognosis was analyzed, respectively. The transwell and scratch experiments were used to detect the effect of PDCD5 on invasion and metastasis of renal cancer cell line A498. The levels of MMP2, MMP9, E-cadherin, N-cadherin and Wnt/β-catenin pathway in A498 cell transfected with PDCD5 were detected by Western blot. Results（1） Compared to the adjacent tissues, PDCD5 expression in RCC was significantly down-regulated（P 〈 0.001）, and was positively correlated with disease stage and prognosis.（2）PDCD5 significantly inhibited the metastasis and invasion in renal cancer cell line A498（P 〈 0.01）.（3）PDCD5 regulated the expression of MMP-2, MMP9, N-cadherin and the key protein in Wnt/β-catenin pathway in A498 cell line and enhanced the expression of E-cadherin. Conclusion PDCD5 regulates the invasion and metastasis by regulating the EMT through Wnt/β-catenin pathway in renal cell carcinoma.