Integrative analyses of biomarkers and pathways for metformin reversing cisplatin resistance in head and neck squamous cell carcinoma cells.

OBJECTIVES

In this study, transcriptome sequencing were performed to elucidate the molecular mechanism by which metformin inhibits head and neck squamous cell carcinoma (HNSCC) cells progression and sensitizes HNSCC cells to chemotherapy. We aimed to propose a novel chemotherapeutic approach with high efficacy and few side effects and provide a new strategy for HNSCC treatment.

DESIGN

The effects of metformin on the biological behaviors of HNSCC cells were validated by CCK8 cell proliferation assays, would healing assays and flow cytometric apoptosis assays. The appropriate metformin concentrations for the experimental pretreatment of HNSCC cells were selected based on experimental results, and the treated cells were subjected to transcriptome sequencing. After bioinformatics analysis and intersection with a post-chemotherapy resistance dataset from the GEO database numbered GSE102787, the genes were identified and used to predict potential metformin targets after functional enrichment analysis.

RESULTS

Metformin significantly inhibited the proliferation and migration and induced the apoptosis of Cal27 and FaDu cells. A total of 284 genes that are potentially targeted by metformin during HNSCC cell sensitization were identified by bioinformatics, and ten hub genes with high connectivity were selected. In particular, Fen1 overexpression was associated with poor prognosis in HNSCC patients.

CONCLUSIONS

Our study demonstrates that Fen1 is overexpressed in HNSCC tissues compared with normal tissues and that Fen1 overexpression is a poor prognostic factor in HNSCC patients. Metformin enhances the ability of cisplatin to inhibit HNSCC progression. Further studies are needed to explore the therapeutic value of Fen1 in HNSCC.