title: Metformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-κB/HIF-1α signal axis.
abstract: Resistance towards chemotherapy is a common complication in treatment of oral cancers, which leads to treatment failure and poor outcome. In recent years, a growing body of evidence has shown that tumour hypoxia significantly contributes to chemoresistance. Metformin, a widely used oral hypoglycaemic drug, can reportedly potentiate the efficacy of chemotherapeutic drugs in various cancers; however, the underlying mechanisms are intricate and have not been fully understood. In this study, we explored the role of metformin in chemosensitivity of oral squamous cell carcinoma cells (OSCC) to cisplatin both in vitro and in vivo, and attempted to elucidate its possible underlying mechanisms. Encouragingly, we found that metformin synergistically enhanced cisplatin cytotoxicity and reversed the chemoresistance to certain extent. This mechanism could likely be related with inhibition of the NF-κB/HIF-1α signal axis and lead to the downregulation of hypoxia-regulated genes products. Therefore, metformin could serve as a chemosensitiser for cisplatin-based regimens for OSCC, thereby providing a theoretical basis for future use in the treatment of oral cancers.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Junqi
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, P.R China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Department of Anesthesia, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, P.R China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing, China.|Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, P.R China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D008687:Metformin / Q000494:pharmacology*; D008819:Mice, Nude; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D008687:Metformin; D002945:Cisplatin