Phenformin inhibits cell proliferation and induces cell apoptosis and autophagy in cholangiocarcinoma
Phenformin inhibits cell proliferation and induces cell apoptosis and autophagy in cholangiocarcinoma
复制标题
苯乙双胍抑制胆管癌细胞增殖并诱导细胞凋亡和自噬
DOI：
10.3892/mmr.2018.8573
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Jiang, Xiaoqing
中科院分区：
文献类型：
--
作者：
Hu, Shuyang;Ouyang, Qing;Jiang, Xiaoqing
胆管癌（CCA）是一种侵袭性恶性肿瘤，晚期患者预后较差。因此，需要寻找新的治疗CCA的药物。本文研究了糖尿病治疗剂苯双胍在CCA细胞株中的生物学效应。细胞计数试剂盒-8细胞活力、细胞克隆形成和皮下肿瘤形成实验表明，苯双胍在体外和体内均能抑制CCA细胞的增殖和生长。此外，苯双胍诱导CCA细胞凋亡和自噬。Phenformin部分激活肝激酶B1 (LKB1)/5 amp激活的蛋白激酶信号通路，对CCA细胞系发挥生物学作用，LKB1的敲低可以逆转这些作用。综上所述，本研究证明了苯双胍在CCA中的生物学效应，并提示苯双胍可能是一种潜在的治疗CCA的新型药物。
Cholangiocarcinoma (CCA) is an aggressive malignant tumor and the prognosis of patients with advanced stage disease remains poor. Therefore, the identification of novel treatment agents for CCA is required. In the present study, the biological effects of the diabetes therapeutic agent, phenformin, in CCA cell lines was investigated. Cell Counting Kit-8 cell viability, cellular clone formation and subcutaneous tumor formation assays were performed, which revealed that phenformin inhibited CCA cell proliferation and growth both in vitro and in vivo. In addition, phenformin induced CCA cell apoptosis and autophagy. Phenformin partly activated the liver kinase B1 (LKB1)/5 AMP-activated protein kinase signaling pathway to exert its biological effects on CCA cell lines, as demonstrated by knockdown of LKB1, which reversed these effects. In conclusion, the present study demonstrated the biological effects of phenformin in CCA and suggested that phenformin may be a potential novel agent for CCA treatment.