PGC-1α诱导细胞周期阻滞抑制肾透明细胞癌的实验研究

PGC-1αInducing cell cycle arrest and inhibiting the progression of renal clear cell carcinoma

目的探讨过氧化物酶体增殖物激活受体γ共激活剂1α(PGC-1α)在透明细胞型肾细胞癌(ccRCC)中的调控作用。方法本研究收集在郑州大学附属第一医院治疗的98例ccRCC患者的肾癌和癌旁组织,以及患者一般临床资料。利用RT-qPCR法检测不同临床分期和病理分级ccRCC患者组织中PGC1αmRNA的相对表达水平。使用细胞培养模型786-O、ACHN、RCC4等ccRCC细胞系以及人肾皮质近曲小管上皮永生化细胞系(HK-2)探讨PGC-1α在肿瘤细胞中的作用。采用CCK8实验、细胞克隆形成实验、细胞周期测定和蛋白表达检测等方法评估PGC-1α对ccRCC细胞增殖、克隆形成能力以及细胞周期的影响及其机制。结果在ccRCC患者中,与癌旁组织相比,癌组织中PGC-1α的表达水平明显下调,并且PGC-1α的表达水平与肿瘤的临床分期和病理分级相关。体外实验结果表明PGC-1α过表达抑制ccRCC细胞的增殖和克隆形成能力,并诱导细胞周期阻滞。进一步的蛋白表达检测显示,PGC-1α过表达导致细胞周期调控相关蛋白的表达水平发生改变,诱导P16、P21和P27的表达的上调和Cyclin D的下调。结论PGC-1α通过诱导细胞周期阻滞从而抑制ccRCC的发展。

Objective To investigate the regulatory role of peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)in clear cell renal cell carcinoma(ccRCC).Methods Ninety-eight ccRCC patients treated at the First Affiliated Hospital of Zhengzhou University were enrolled,and their cancerous and adjacent tissues were collected along with general clinical data.The relative expression levels of PGC1αmRNA in ccRCC tissues at different clinical stages and pathological grades were detected using RT-qPCR.The role of PGC-1αin tumor cells was explored using cell culture models including ccRCC cell lines 786-O,ACHN,RCC4,and human renal cortex proximal tubule epithelial immortalized cell line(HK-2).Cell proliferation,colony formation ability,and cell cycle were assessed using CCK8 assay,colony formation assay,cell cycle analysis,and protein expression detection to evaluate the impact of PGC-1αon ccRCC cells and its underlying mechanisms.Results PGC-1αexpression was significantly downregulated in ccRCC tissues compared to adjacent tissues in patients,and its expression levels were correlated with tumor clinical stage and pathological grade.In vitro experiments revealed that overexpression of PGC-1αinhibited ccRCC cell proliferation and colony formation ability,inducing cell cycle arrest.Further protein expression analysis showed that overexpression of PGC-1αaltered the expression levels of cell cycle-related proteins,upregulating P16,P21,and P27 expression,while downregulating Cyclin D expression.Conclusion PGC-1αinhibits the development of ccRCC by inducing cell cycle arrest.