Xia Yan, Liu Xianhao, Liu Beibei, Zhang Xiaoshi, Tian Geng
Department of Biotherapy Research Center, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Department of Oncology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518035, P.R. China.
Exp Ther Med. 2018 Apr;15(4):4047-4055. doi: 10.3892/etm.2018.5905. Epub 2018 Feb 28.
Liver cancer is an aggressive malignancy with a very high fatality rate. Although megestrol acetate (MA) and arsenic trioxide (ATO) have shown an antitumor effect in liver cancer cells, the therapeutic benefits of MA or ATO alone in patients with liver cancer were limited. The aim of the present study was to elucidate whether the co-treatment of MA/ATO could enhance antitumor efficacy in liver cancer cell lines (Hep G2 and BEL 7402) and explore the underlying anti-cancer mechanisms. The cell viability, apoptotic response and expression levels of associated proteins were detected by Cell Counting Kit-8 assay, flow cytometry and western blotting, respectively. An xenograft model in nude mice bearing a Hep G2 tumor was used to estimate tumor growth . Co-treatment with MA/ATO markedly improved the inhibition of cell viability, enhanced apoptosis, and increased the phosphorylation of p38, c-Jun N-terminal kinase 1/2 and extracellular signal-regulated kinase 1/2 on liver cancer cell lines. Furthermore, the tumor growth in the murine Hep G2 cancer xenograft model was significantly inhibited by combined treatment with MA/ATO. The results indicated that MA/ATO combined treatment enhanced antitumor efficacy and possessed potential application for treating liver cancer.
肝癌是一种侵袭性恶性肿瘤,死亡率极高。尽管醋酸甲地孕酮(MA)和三氧化二砷(ATO)已在肝癌细胞中显示出抗肿瘤作用,但MA或ATO单独用于肝癌患者的治疗效果有限。本研究的目的是阐明MA/ATO联合治疗是否能增强肝癌细胞系(Hep G2和BEL 7402)的抗肿瘤疗效,并探索其潜在的抗癌机制。分别通过细胞计数试剂盒-8法、流式细胞术和蛋白质印迹法检测细胞活力、凋亡反应及相关蛋白的表达水平。采用携带Hep G2肿瘤的裸鼠异种移植模型评估肿瘤生长情况。MA/ATO联合治疗显著提高了对肝癌细胞系细胞活力的抑制作用,增强了细胞凋亡,并增加了p38、c-Jun氨基末端激酶1/2和细胞外信号调节激酶1/2的磷酸化水平。此外,MA/ATO联合治疗显著抑制了小鼠Hep G2癌异种移植模型中的肿瘤生长。结果表明,MA/ATO联合治疗增强了抗肿瘤疗效,在肝癌治疗中具有潜在的应用价值。