title: Cisplatin combined with metformin inhibits migration and invasion of human nasopharyngeal carcinoma cells by regulating E-cadherin and MMP-9.
abstract: Metformin has been shown to be useful in reducing insulin resistance by restoring sensitivity. Recent evidence suggests that metformin might also possess anti-tumour activity. This study aimed to investigate the effects of cisplatin combined with metformin on the proliferation, invasion and migration of HNE1/DDP human nasopharyngeal carcinoma (NPC) cells, and to provide a new target for treating metastasis. The MTT assay was used to assess viability of HNE1/DDP cells after exposure to different concentrations of 2, 5-diaminopyrimidine-4, 6-diol (DDP; 2, 4, 8, 16, and 32 μmol·L(-1)), metformin (5, 10, 15, 20, and 25 μmol·L(-1)), and 4 μmol·L(-1) of DDP combined with metformin. Wound healing and transwell migration assays were performed to assess cell migration and invasion, and expression of E-cadherin and MMP-9 was detected using Western blotting. MTT assay results showed that DDP could inhibit the proliferation of HNE1/DDP cells in a time- and concentration-dependent manner, with an IC50 of 32.0 μmol·L(-1) at 24 h (P < 0.05), whereas low concentrations of DDP had almost no inhibitory effects on cell invasion and migration. DDP combined with metformin significantly inhibited cell invasion and migration. In addition, genes related to migration and invasion, such as those of E-cadherin and MMP-9, showed differential expression in the NPC cell line HNE1/DDP. In the present study, with an increasing concentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin was significantly upregulated. Taken together, our results show that cisplatin combined with metformin has effects on proliferation, invasion, and migration of human NPC cells.
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui, China E-mail : liuhao6886@foxmail.com.
authors.forename: Xiao-Jin
authors.initials: XJ
authors.lastname: Sun
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.forename: Hai-Hui
authors.initials: HH
authors.lastname: Li
authors.forename: Zhi-Wen
authors.initials: ZW
authors.lastname: Jiang
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Jiang
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015820:Cadherins / Q000096:biosynthesis; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008687:Metformin / Q000494:pharmacology*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D007004:Hypoglycemic Agents; D008687:Metformin; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin