靶向癌细胞代谢：二甲双胍与2-脱氧葡萄糖联合通过p38丝裂原活化蛋白激酶/应激活化蛋白激酶信号通路调节卵巢癌细胞凋亡。
Targeting cancer cell metabolism: The combination of metformin and 2-Deoxyglucose regulates apoptosis in ovarian cancer cells via p38 MAPK/JNK signaling pathway.
作者信息
Zhu Jie, Zheng Ya, Zhang Haiyan, Sun Hong
机构信息
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai 200011, China.
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University Shanghai 200011, China.
出版信息
Am J Transl Res. 2016 Nov 15;8(11):4812-4821. eCollection 2016.
Abstract
Targeting cancer cell metabolism is a new promising strategy to fight cancer. Metformin, a first-line treatment for type 2 diabetes mellitus, exerts anti-cancer and anti-proliferative action. 2-deoxyglucose (2-DG), a glucose analog, works as a competitive inhibitor of glycolysis. In this study, we show for the first time that metformin in combination with 2-DG inhibited growth, migration, invasion and induced cell cycle arrest of ovarian cancer cells in vitro. Moreover, metformin and 2-DG could efficiently induce apoptosis in ovarian cancer cells, which was achieved by activating p38 MAPK and JNK pathways. Our study reinforces the growing interest of metabolic interference in cancer therapy and highlights the potential use of the combination of metformin and 2-DG as an anti-tumor treatment in ovarian cancer.
摘要
靶向癌细胞代谢是一种对抗癌症的新的有前景的策略。二甲双胍是2型糖尿病的一线治疗药物，具有抗癌和抗增殖作用。2-脱氧葡萄糖（2-DG）是一种葡萄糖类似物，作为糖酵解的竞争性抑制剂发挥作用。在本研究中，我们首次表明二甲双胍与2-DG联合使用可在体外抑制卵巢癌细胞的生长、迁移、侵袭并诱导细胞周期停滞。此外，二甲双胍和2-DG可有效诱导卵巢癌细胞凋亡，这是通过激活p38丝裂原活化蛋白激酶（MAPK）和应激活化蛋白激酶（JNK）途径实现的。我们的研究强化了代谢干扰在癌症治疗中日益增长的关注度，并突出了二甲双胍与2-DG联合作为卵巢癌抗肿瘤治疗方法的潜在用途。
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