靶向缺氧诱导因子-1α（HIF-1α）是细胞对二氯乙酸（DCA）和二甲双胍敏感的前提条件。
Targeting HIF-1α is a prerequisite for cell sensitivity to dichloroacetate (DCA) and metformin.
作者信息
Hong Sung-Eun, Jin Hyeon-Ok, Kim Hyun-Ah, Seong Min-Ki, Kim Eun-Kyu, Ye Sang-Kyu, Choe Tae-Boo, Lee Jin Kyung, Kim Jong-Il, Park In-Chul, Noh Woo Chul
机构信息
Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea.
出版信息
Biochem Biophys Res Commun. 2016 Jan 8;469(2):164-70. doi: 10.1016/j.bbrc.2015.11.088. Epub 2015 Nov 23.
Recently, targeting deregulated energy metabolism is an emerging strategy for cancer therapy. In the present study, combination of DCA and metformin markedly induced cell death, compared with each drug alone. Furthermore, the expression levels of glycolytic enzymes including HK2, LDHA and ENO1 were downregulated by two drugs. Interestingly, HIF-1α activation markedly suppressed DCA/metformin-induced cell death and recovered the expressions of glycolytic enzymes that were decreased by two drugs. Based on these findings, we propose that targeting HIF-1α is necessary for cancer metabolism targeted therapy.
最近，针对能量代谢失调进行靶向治疗是一种新兴的癌症治疗策略。在本研究中，与单独使用每种药物相比，二氯乙酸（DCA）和二甲双胍联合使用显著诱导细胞死亡。此外，包括己糖激酶2（HK2）、乳酸脱氢酶A（LDHA）和烯醇化酶1（ENO1）在内的糖酵解酶的表达水平被这两种药物下调。有趣的是，缺氧诱导因子-1α（HIF-1α）的激活显著抑制了DCA/二甲双胍诱导的细胞死亡，并恢复了被这两种药物降低的糖酵解酶的表达。基于这些发现，我们提出针对HIF-1α进行靶向治疗对于癌症代谢靶向治疗是必要的。
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