陆军军医大学学报2026，Vol.48Issue(6)：701-708,8.DOI:10.16016/j.2097-0927.202511068
缺氧诱导因子-2α经转化生长因子-β2促进胶质母细胞瘤细胞化疗抵抗
Hypoxia-inducible factor-2α promotes chemoresistance in glioblastoma cells via transforming growth factor-β2
摘要
Abstract
Objective Hypoxia in the tumor microenvironment is a critical factor contributing to chemoresistance in glioblastoma.This study preliminarily investigates the role of hypoxia-inducible factor-2α(HIF-2α)and transforming growth factor-β2(TGF-β2)in promoting chemotherapy resistance of glioblastoma cells under hypoxic conditions.Methods U87 and U118 cells(n=3)were cultured under normoxic and hypoxic conditions and treated with temozolomide(TMZ)for 24,48,and 72 h.Cell proliferation was assessed by CCK-8 assay,and apoptosis was detected by flow cytometry after 48 h of culture.Using normoxic culture as control,U87 and U118 cells(n=3)were subjected to hypoxic culture for 4,8,12,and 24 h,followed by RT-qPCR to measure HIF-2α and TGF-β2 mRNA expression.After further hypoxic culture for 12,24,and 48 h,the protein levels of HIF-2α and TGF-β2 were detected by Western blotting.After knockdown of HIF-2α and TGF-β2,the cells(n=3)were cultured under hypoxia and treated with TMZ for 24,48,and 72 h.Then,the cell proliferation was detected by CCK-8 assay.After 24 h of culture,TGF-β2(50 ng/mL)was added to the culture medium of some cells,and the cells were further cultured under hypoxia for another 24 h,followed by flow cytometry for cell apoptosis.Western blotting was applied to detect TGF-β2 expression in HIF-2α knockdown cells after 48 h of hypoxic culture.Results CCK-8 and flow cytometry assays indicated that the hypoxia+TMZ group showed increased cell viability(P<0.05)and decreased apoptotic rate compared to the normoxia+TMZ group(P<0.05).RT-qPCR revealed that compared with the normoxia group,the expression levels of HIF-2α and TGF-β2 in hypoxia-cultured cells gradually increased with the prolongation of hypoxic time(P<0.05),and Western blotting also confirmed that the protein expression of HIF-2α and TGF-β2 increased in a time-dependent manner after hypoxic culture.Lower cell viability(P<0.05)and higher apoptotic rate(P<0.05)were observed in the HIF-2α-knockdown and TGF-β2-knockdown cells compared with the control non-knockdown group.Continued hypoxic culture of HIF-2α-knockdown cells indicated decreased TGF-β2 expression compared with the control non-knockdown HIF-2α group.Conclusion HIF-2α chemoresistance in glioblastoma cells via TGF-β2.关键词
胶质母细胞瘤/缺氧/缺氧诱导因子-2α/转化生长因子-β2Key words
glioblastoma/hypoxia/hypoxia-inducible factor-2α/transforming growth factor-β2分类
医药卫生引用本文复制引用
赵璐,汪攀,龚胜,廖彬,吴南..缺氧诱导因子-2α经转化生长因子-β2促进胶质母细胞瘤细胞化疗抵抗[J].陆军军医大学学报,2026,48(6):701-708,8.基金项目
国家自然科学基金面上项目(82473430) （82473430）
重庆市科卫联合医学科研项目重大项目(2023DBXM004) （2023DBXM004）
重庆市科卫联合医学科研青年项目(2023QNXM043) Supported by the General Program of National Natural Science Foundation of China(82473430),the Major Joint Medical Research Project of Chongqing Science and Technology Commission and Chongqing Health Commission(2023DBXM004),and the Joint Youth Medical Research Project of Chongqing Science and Technology Commission and Chongqing Health Commission Chongqing(2023QNXM043). （2023QNXM043）
