Down-regulation of BAG3 inhibits proliferation and promotes apoptosis of glioblastoma multiforme through BAG3/HSP70/HIF-1α signaling pathway

被引:0
作者
Li, Jiqiang [1 ,2 ]
Chen, Qianxue [2 ]
Xu, Shuwen [3 ]
Wu, Jinglei [1 ]
Huang, Qiaochun [1 ]
Song, Ping [1 ]
Duan, Faliang [1 ]
机构
[1] Wuhan 1 Hosp, Dept Neurosurg, 215 Zhongshan Ave, Wuhan 430022, Hubei, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Neurosurg, Wuhan, Hubei, Peoples R China
[3] Wuhan Univ, Renmin Hosp, Clin Lab, Wuhan, Hubei, Peoples R China
基金
中国国家自然科学基金;
关键词
Bcl2-associated athanogene 3 (BAG3); hypoxia inducible factor 1 alpha (HIF-1 alpha); heat shock protein 70 (HSP70); proliferation; apoptosis; glioblastoma multiforme; CANCER CELLS; HYPOXIA; HIF-1-ALPHA; EXPRESSION; FACTOR-1; PROTEIN; TARGET; ALPHA; MODULATION; CARCINOMA;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Bcl2-associated athanogene 3 (BAG3) belongs to the BAG family and regulates many biologic behaviors of tumors. When tumor cells are in a hypoxic condition, BAG3 protein expression level increases, as does HIF-1 alpha which is an important transcription factor induced by hypoxia. Glioblastoma is one of the typical solid tumors existing in a hypoxic microenvironment that can activate expression of BAG3 and HIF-1 alpha. This research aimed to reveal the relationship between BAG3 and HIF-1 alpha and their effects in glioblastoma multiforme. We found that down-regulated BAG3 inhibited proliferation and promoted apoptosis of glioblastoma multiforme U87 and U251 cell lines by decreasing HIF-1 alpha expression level. The mechanism of BAG3 regulating HIF-1 alpha is mainly through increasing degradation of HIF-1 alpha by HSP70. When HIF-1 alpha was up-regulated, induced by HIF-1 alpha plasmid transfection on the basis of down-regulation of BAG3, the proliferation inhibition and apoptosis promotion were partially reversed. This novel result showed, for the first time, that down-regulation of BAG3 resulted in a low expression of HIF-1 alpha under both normoxic or hypoxic conditions and finally caused inhibited proliferation and promoted apoptosis in glioblastoma. The mechanism of down-regulated BAG3 decreased HIF-1 alpha protein expression through enhancing formation of HSP70-HIF-1 alpha complex and promoting degradation of HIF-1 alpha by HSP70.
引用
收藏
页码:4305 / 4318
页数:14
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