缺氧条件下HIF-1α调节CXCR4、CXCR7表达对肾癌细胞侵袭和迁移作用的影响  

The effect of HIF-1 under hypoxic conditionsαregulating the expression of CXCR4 and CXCR7 on the invasion and migration of renal cancer cells

作　　者：陈伟 何屹 金晶 顾燕琴 曹益方 Chen Wei

机构地区：[1]嘉兴学院附属医院,314000

出　　处：《浙江临床医学》2023年第12期1770-1772,1776,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省嘉兴市公益性研究计划项目(2020AD30059);嘉兴市医学重点学科建设项目(2023-ZC-013)。

摘　　要：目的探讨缺氧条件下缺氧诱导因子1α(HIF-1α)对趋化因子受体CXCR4和CXCR7表达的调节及其对肾癌A498细胞侵袭迁移作用的影响。方法将肾癌A498细胞分别置于正常含氧(20%O_(2))和缺氧(1%O_(2))环境下培养,分为正常含氧组和缺氧组。利用qPCR和流式细胞术检测两组细胞CXCR4和CXCR7mRNA和蛋白水平。检测缺氧组A498细胞敲减HIF-1α后CXCR4和CXCR7mRNA和蛋白水平的变化情况。利用Transwell和划痕实验检测敲减CXCR4或CXCR7后两组A498细胞侵袭和迁移能力的变化情况。结果与正常含氧组相比,缺氧刺激下肾癌A498细胞CXCR4和CXCR7mRNA和蛋白含量均明显升高(P<0.01)。敲除HIF-1α后,A498细胞CXCR4和CXCR7mRNA和蛋白含量则明显降低(P<0.01)。缺氧条件下A498细胞的侵袭和迁移能力显著升高(P<0.01),敲减CXCR4或CXCR7后侵袭和迁移能力则显著降低(P<0.01)。结论缺氧环境下HIF-1α能够提高A498细胞CXCR4及CXCR7的表达,促进细胞的侵袭和迁移,这一结果为临床制定转移性肾癌治疗策略提供了新思路。Objective To explore the regulation of hypoxia-inducible factor-1α(HIF-1α)on the expression of chemokine receptors CXCR4 and CXCR7 under hypoxic conditions and impact on the invasion and migration ability of renal cancer cells.Methods Renal cancer cells A498 were divided into the normal oxygen and the hypoxic group,and were cultured in 20%O_(2)and 1%O_(2)environments respectively.The mRNA and protein levels of CXCR4 and CXCR7 in two groups of cells were detected using qPCR and flow cytometry.The changes of mRNA and protein levels of CXCR4 and CXCR7 in A498 cells were detected after HIF-1αknockdown in the hypoxic group.The changes of the invasion and migration ability of A498 cells in both groups were tested after knockdown of CXCR4 or CXCR7.Results Compared with the normal oxygen group,the mRNA and protein levels of CXCR4 and CXCR7 in A498 cells were significantly increased under hypoxia stimulation.The mRNA and protein contents of CXCR4 and CXCR7 in A498 cells were significantly reduced after HIF-1αknocked down.Under hypoxic conditions,the invasion and migration ability of A498 cells was significantly increased,while after knocking down CXCR4 or CXCR7,the invasion and migration ability was significantly reduced.Conclusion HIF-1αcan increase the expression of CXCR4 and CXCR7 in renal cancer A498 cells in hypoxic environments,and promote the invasion and migration of renal cancer cells.The results provide new ideas for clinical development of treatment strategies for metastatic renal cancer.

关 键 词：缺氧 缺氧诱导因子1Α CXCR4 CXCR7 肾细胞癌 

分 类 号：R737.11[医药卫生—肿瘤]