Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410006, P.R. China.
Department of Radiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
Int J Biol Sci. 2019 Sep 7;15(11):2497-2508. doi: 10.7150/ijbs.37481. eCollection 2019.
Deregulation of glycolysis is a common phenomenon in human colorectal cancer (CRC). In the present study, we reported that Hexokinase 2 (HK2) is overexpressed in human CRC tissues and cell lines, knockout of HK2 inhibited cell proliferation, colony formation, and xenograft tumor growth. We demonstrated that the natural compound, xanthohumol, has a profound anti-tumor effect on CRC via down-regulation of HK2 and glycolysis. Xanthohumol suppressed CRC cell growth both and . Treatment with xanthohumol promoted the release of cytochrome C and activated the intrinsic apoptosis pathway. Moreover, our results revealed that xanthohumol down-regulated the EGFR-Akt signaling, exogenous overexpression of constitutively activated Akt1 significantly impaired xanthohumol-induced glycolysis suppression and apoptosis induction. Our results suggest that targeting HK2 appears to be a new approach for clinical CRC prevention or treatment.
糖酵解的失调是人类结直肠癌（CRC）的一种常见现象。在本研究中，我们报道了己糖激酶 2（HK2）在人 CRC 组织和细胞系中过表达，敲除 HK2 抑制了细胞增殖、集落形成和异种移植肿瘤生长。我们证明了天然化合物黄腐酚通过下调 HK2 和糖酵解对 CRC 具有显著的抗肿瘤作用。黄腐酚抑制 CRC 细胞生长 both 和. 用黄腐酚处理可促进细胞色素 C 的释放并激活内在凋亡途径。此外，我们的结果表明，黄腐酚下调了 EGFR-Akt 信号通路，外源性过表达组成型激活的 Akt1 显著削弱了黄腐酚诱导的糖酵解抑制和凋亡诱导作用。我们的研究结果表明，靶向 HK2 似乎是 CRC 临床预防或治疗的一种新方法。
