Research Of Metformin Sensitizing The Response Of Oral Squamous Cell Carcinoma To Cisplatin Treatment

BackgroundResistance towards chemotherapy is a common complication in the treatment of oral cancers,which leads to treatment failure and poor outcome.In recent years,a growing body of evidence has shown that HIF-la which existing tumour hypoxia significantly contributes to chemoresistance.Recent studies have validated a close connection between HIF-1? expression and chemoresistance in multiple malignancies.Another characteristic feature of the tumour microenvironment is inflammation.An essential element responsible for the regulation of inflammatory response is nuclear factor-kappa B(NF-?B).It is evident that a crosstalk does exist between these two key molecular players involved in hypoxia and inflammation.In our previous study,we proved that NF-?B was located upstream of the HIF-1? promoter,with the function of regulating HIF-1? transcription,which was fairly consistent with some of the previous studies.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,thereby providing a theoretical basis for future use in the treatment of oral cancers.PurposeWhether Metformin could sensitize the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-kB/HIF-1? signal axisMethods1.To detect cisplatin IC50 values of OSCC under hypoxia via MTT cell viability assay2.To detect the expression of HIF-1? under hypoxia and IC50 values after being treated with si-HIF-1?3.OSCC cells were treated with Metformin and cisplatin,cell apoptosis was detected by Annexin V-FITC Apoptosis Detection Kit.4.Immunofluorescence was used to detect the efficacy of Metformin on regulating the expression and function of p655.To detect the ability of Metformin enhancing the chemotherapy efficacy of cisplatin in vivoResults1.Cisplatin IC50 values of OSCC cells under hypoxia were significantly increased.2.The expression of HIF-1? under hypoxia was increased and IC50 values were decreased after being treated with si-HIF-1?3.The rate of apoptotic cells was significantly increased after being treated with Metformin4.Metformin inhibits the activation of p655.Metformin decreases the expression of HIF-la,GLUT-1,Bcl-2,p-p65 in vivoConclusionMetformin sensitizes the response of oral squamous cell carcinoma to cisplatin treatment through inhibition of NF-?B/HIF-1? signal axis...