二甲双胍
KLF4公司
顺铂
癌症研究
细胞凋亡
医学
化疗
癌症
细胞
癌症干细胞
药理学
肿瘤科
生物
内科学
胚胎干细胞
诱导多能干细胞
生物化学
胰岛素
基因
遗传学
作者
Tong Zhou,Xuefeng Zhang,Dan Yang,Weideng Wei,Jianguo Gan,Xiaoqiang Xia,Xinjian Ye,Jian Jiang,Xiaodong Feng
摘要
Abstract Objective Chemoresistance is a common event after chemotherapy, including oral squamous cell carcinoma (OSCC). Accumulated evidence suggests that the cancer stemness significantly contributes to therapy resistance. An unresolved question remains regarding how to effectively overcome OSCC chemoresistance by targeting stemness. This study aims to investigate the antitumor effect of metformin and clarify the potential molecular mechanisms. Methods Cellular models resistant to chemotherapy were established, and their viability and sphere‐forming ability were assessed using CCK‐8 and soft agar formation assays, respectively. RNA‐seq and Western blotting analyses were employed to delve into the molecular pathways. Furthermore, to corroborate the inhibitory effects of metformin and cisplatin at an animal level, a subcutaneous tumor transplantation model was instituted. Results Metformin as a monotherapy exhibited inhibition of stemness traits via Krüppel‐like factor 4 (KLF4). Metformin and cisplatin can synergically inhibit cell proliferation and induce cell apoptosis. Animal experiments confirmed the inhibitory effect of cisplatin and metformin on tumor in mice. Conclusion Our study proposes a potential therapeutic approach of combining chemotherapy with metformin to overcome chemoresistance in OSCC.
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