Zheng Jiasheng, Li Cong, Wu Xia, Liu Mengmeng, Sun Xicai, Yang Yingzhuo, Hao Meijun, Sheng Shoupeng, Sun Yu, Zhang Honghai, Long Jiang, Liang Yi, Hu Caixia
Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing, 100069, China,
Tumour Biol. 2014 May;35(5):4219-24. doi: 10.1007/s13277-013-1552-y. Epub 2013 Dec 29.
Astrocyte elevated gene-1 (AEG-1) is an important force in the development and progression of hepatocellular carcinoma (HCC). To extend our study, we examined here the role of AEG-1 in anti-metastatic effects of Huaier polysaccharide (HP) on the human HCC MHCC97-H cell line. AEG-1 shRNA contributed to the anti-proliferation effect of HP on MHCC97-H cells. Furthermore, results of Transwell insert chambers showed that low expression of AEG-1 could effectively facilitate HP to suppress MHCC97-H cell migration and invasion. We achieved this by reducing phosphoinositide 3-kinases (P13K) and phosphorylated Akt (pAkt) expression as well as enhancing natural killer (NK) cell activity. Taken together, our data strongly suggested that AEG-1 shRNA could block the carcinogenesis and progression of MHCC97-H cells and highlight the therapeutic potential of HP in HCC treatment, at least by part, by inhibiting the activation of the PI3K/Akt pathway and enhancing the NK cell-mediated immune response. These findings may provide a new strategy for HCC treatment.
星形胶质细胞上调基因-1(AEG-1)是肝细胞癌(HCC)发生发展过程中的一种重要力量。为了拓展我们的研究,我们在此研究了AEG-1在槐耳多糖(HP)对人肝癌MHCC97-H细胞系的抗转移作用中的角色。AEG-1短发夹RNA(shRNA)有助于HP对MHCC97-H细胞的抗增殖作用。此外,Transwell小室实验结果表明,AEG-1的低表达能够有效促进HP抑制MHCC97-H细胞的迁移和侵袭。我们通过降低磷酸肌醇3-激酶(PI3K)和磷酸化蛋白激酶B(pAkt)的表达以及增强自然杀伤(NK)细胞活性来实现这一点。综上所述,我们的数据强烈表明,AEG-1 shRNA可以阻断MHCC97-H细胞的癌变和进展,并突出了HP在HCC治疗中的治疗潜力,至少部分是通过抑制PI3K/Akt途径的激活和增强NK细胞介导的免疫反应来实现的。这些发现可能为HCC治疗提供一种新策略。