下调HIF-1α/PLOD2信号通路对缺氧肾透明细胞癌786-0和ACHN细胞株增殖、迁移和侵袭的影响  

Effect of Down-regulation of HIF-1α/PLOD2 Signaling Pathway on Migration,Invasion and Proliferation of Renal Clear Cell Carcinoma Cells 786-0 and ACHN under Hypoxia

作　　者：曹雪 杨金成[2] 李媛 赵梦潮 赵天琪 苗冬青 侯绍章 CAO Xue;YANG Jincheng;LI Yuan;ZHAO Mengchao;ZHAO Tianqi;MIAO Dongqing;HOU Shaozhang(Department of Pathology,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China;The First People’s Hospital of Yinchuan,Second Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China;Department of Pharmacy,General Hospital of Ningxia Medical University,First Clinical Medical College of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学基础医学院病理学系,银川750004 [2]银川市第一人民医院,宁夏医科大学第二临床医学院,银川750004 [3]宁夏医科大学总医院药剂科,宁夏医科大学第一临床医学院,银川750004

出　　处：《宁夏医科大学学报》2023年第10期973-978,1014,共7页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金项目(2021AAC03512)。

摘　　要：目的 探讨缺氧条件下缺氧诱导因子1α(HIF-1α)影响肾透明细胞癌(ccRCC)细胞迁移、侵袭和增殖的机制。方法 体外培养人ccRCC细胞,分为正常对照组(NG组)、缺氧组(Hypoxia组,1%O2)和缺氧+HIF-1α抑制剂组(Hypoxia+PX-478组,55μmol·L-1/45μmol·L-1)。用CCK-8法检测细胞活力;用Western blot实验检测各组ccRCC细胞中HIF-1α、2-酮戊二酸5-双加氧酶2(PLOD2)蛋白表达量;用细胞划痕实验检测ccRCC细胞迁移能力;用Transwell实验检测ccRCC细胞迁移、侵袭能力;用克隆形成实验检测ccRCC细胞增殖能力。结果 HIF-1α抑制剂加入后的细胞活力降低,且随着药物浓度升高而降低;与NG组相比,Hypoxia组HIF-1α、PLOD2蛋白表达量均增加(P均<0.05),与Hypoxia组相比,Hypoxia+PX-478组HIF-1α、PLOD2蛋白表达量发均降低(P均<0.05);与NG组相比,Hypoxia组ccRCC细胞786-0的迁移、侵袭和增殖能力均提高(P均<0.01),与Hypoxia组相比,Hypoxia+PX-478组细胞的迁移、侵袭和增殖能力均降低(P均<0.01)。结论 缺氧条件下,下调HIF-1α/PLOD2通路可抑制786-0和ACHN细胞的迁移、侵袭和增殖。Objective To investigate how hypoxia-inducible factor 1α(HIF-1α)affects the migration,invasion and proliferation of clear cell kidney cancer(ccRCC)cells under hypoxic conditions.Methods Human kidney cancer cells cultured in vitro were divided into normal control(NG),Hypoxia(hypoxia,1%O2)and Hypoxia+HIF-1αinhibitor(hypoxia+PX-478,55μmol·L-1/45μmol·L-1)groups.Cell viability was measured by CCK8,and HIF-1αand PLOD2 protein expression levels in each kidney cancer cell group were determined by Western blot analysis.Migration capacity of kidney cancer cells was determined by cell scraping and transwell assay.The invasion capacity was determined by transwell assay.The proliferation capacity was determined by clonogenic assay.Results The viability of renal carcinoma cells decreased significantly after the addition of HIF-1αinhibitor and decreased with increasing of drug concentration.The protein expression of HIF-1αand PLOD2 were significantly increased in the Hypoxia group compared with the NG group(P all<0.05),while the protein expression of HIF-1αand PLOD2 were significantly decreased in the Hypoxia+PX-478 group compared with the Hypoxia group(P all<0.05),and the migration,invasion and proliferation ability of kidney cancer cells 786-0 were significantly improved in the Hypoxia group compared with the NG group(P all<0.01).The migration,invasion and proliferation ability of cells in the hypoxia+PX-478 group were significantly decreased compared with the Hypoxia group(P all<0.01).Conclusion Down-regulation of the HIF-1α/PLOD2 pathway inhibits migration,invasion and proliferation of 786-0 and ACHN cells under hypoxic conditions.

关 键 词：缺氧 肾透明细胞癌 缺氧诱导因子1Α 2-酮戊二酸5-双加氧酶2 

分 类 号：R737.1[医药卫生—肿瘤]