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. Recentevidence suggests that metformin might also possess anti-tumour activity. This study aimed to investigate theeffects of cisplatin combined with metformin on the proliferation, invasion and migration of HNE1/DDP humannasopharyngeal carcinoma (NPC) cells, and to provide a new target for treating metastasis. The MTT assay wasused 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 DDPcombined with metformin. Wound healing and transwell migration assays were performed to assess cell migrationand invasion, and expression of E-cadherin and MMP-9 was detected using Western blotting. MTT assay resultsshowed that DDP could inhibit the proliferation of HNE1/DDP cells in a time- and concentration-dependentmanner, with an IC50 of 32.0 μmol·L-1 at 24 h (P < 0.05), whereas low concentrations of DDP had almost noinhibitory effects on cell invasion and migration. DDP combined with metformin significantly inhibited cellinvasion and migration. In addition, genes related to migration and invasion, such as those of E-cadherin andMMP-9, showed differential expression in the NPC cell line HNE1/DDP. In the present study, with an increasingconcentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin wassignificantly upregulated. Taken together, our results show that cisplatin combined with metformin has effectson proliferation, invasion, and migration of human NPC cells.