Wang Fan, Dai Weiqi, Wang Yugang, Shen Miao, Chen Kan, Cheng Ping, Zhang Yan, Wang Chengfen, Li Jingjing, Zheng Yuanyuan, Lu Jie, Yang Jing, Zhu Rong, Zhang Huawei, Zhou Yingqun, Xu Ling, Guo Chuanyong
Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai, PR China.
Department of Gastroenterology, Shanghai Tongren Hospital, Jiaotong University of Medicine, Shanghai, PR China.
PLoS One. 2014 May 9;9(5):e97414. doi: 10.1371/journal.pone.0097414. eCollection 2014.
Hepatocellular carcinoma (HCC) is one of the few cancers in which a continuous increase in incidence has been observed over several years. Drug resistance is a major problem in the treatment of HCC. In the present study, we used salinomycin (Sal) and 5-fluorouracil (5-FU) combination therapy on HCC cell lines Huh7, LM3 and SMMC-7721 and nude mice subcutaneously tumor model to study whether Sal could increase the sensitivity of hepatoma cells to the traditional chemotherapeutic agent such as 5-FU. The combination of Sal and 5-FU resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. Sal reversed the 5-FU-induced increase in CD133(+) EPCAM(+) cells, epithelial-mesenchymal transition and activation of the Wnt/β-catenin signaling pathway. The combination of Sal and 5-FU may provide us with a new approach to reverse drug resistant for the treatment of patients with HCC.
肝细胞癌（HCC）是少数几种在数年中发病率持续上升的癌症之一。耐药性是HCC治疗中的一个主要问题。在本研究中，我们对肝癌细胞系Huh7、LM3和SMMC-7721以及裸鼠皮下肿瘤模型采用沙利霉素（Sal）和5-氟尿嘧啶（5-FU）联合治疗，以研究Sal是否能增加肝癌细胞对传统化疗药物如5-FU的敏感性。Sal和5-FU联合使用在体外和体内均对肝肿瘤产生协同抗肿瘤作用。Sal逆转了5-FU诱导的CD133(+)EPCAM(+)细胞增加、上皮-间质转化以及Wnt/β-连环蛋白信号通路的激活。Sal和5-FU联合使用可能为我们提供一种逆转耐药性以治疗HCC患者的新方法。
