The Radiosensitivity Increasing Effect By Inhibiting Glucose Metabolism Enzyme LDHA Activity Towards Gastric Cancer

Objective: This research sought to ascertain if LDHA inhibition could enhance the effectiveness of radiotherapy for gastric cancer,and to initially investigate its molecular structure.Assessing the effect of LDHA expression on gastric cancer prognosis is also necessary.Methods: In this study,we used GEPIA,UALCAN and HPA online database technologies to detect LDHA expression at mRNA and protein levels in gastric cancer(GC),analyze the correlation between LDHA mRNA expression levels and tumor stage of gastric adenocarcinoma patients and the correlation with gene expression of glycolytic markers.The prognostic value of LDHA was evaluated using the KaplanMeier mapper database.We conducted a study to investigate the correlation between LDHA expression and the degree of immune cell infiltration in gastric cancer,as well as the prognostic effect of varying levels of immune cell infiltration in tumors on gastric adenocarcinoma patients.The TIMER database was utilized.ELDHA was utilized as a potential gene to investigate if inhibiting LDHA could augment the effect of radiotherapy on gastric cancer,as well as assess the effect of LDHA expression on the prognosis of gastric cancer.By utilizing q RT-PCR at the mRNA level,we screened gastric cancer cells HGC-27 and AGS with high LDHA expression and further validated the expression of LDHA in these cells through the HPA database for in vitro experiments.After treating 2 gastric cancer cell lines with different concentrations of LDHA inhibitor sodium oxamate for 24 h,the IC50 values of the cells were determined by the CCK8 method.We scrutinized the clonogenic capacity.The pre-treatment of HGC-27 and AGS cells with sodium oxamate and the exposure to a particular dose of X-rays were used to assess their proliferation capacity and sensitivity to radiotherapy for gastric cancer.Exploring the inhibitory impact of LDHA’s high expression on gastric cancer radiotherapy sensitivity,we used the plate clone formation assay and CCK8 assay.To investigate the sensitizing effect of LDHA inhibition on gastric cancer radiation therapy.Results: LDHA expression was discovered to be augmented in gastric cancer,a prognostic factor that is linked to radiotherapy.However,sodium oxamate inhibition of LDHA significantly improved the radiosensitivity of HGC-27 and AGS gastric cancer cells,as well as the ionizing radiation-induced cell killing effect and decreased their proliferation and colony-forming capacity,potentially increasing their sensitivity to radiotherapy.Conclusions: In gastric cancer,LDHA is a potential target for treatment and is also associated with radiosensitivity.Inhibiting LDHA activity may increase the radiosensitivity of gastric cancer cell in vitro.The efficacy of radiotherapy for gastric cancer patients is anticipated to be enhanced by the inhibition of LDHA activity,making it a promising therapeutic strategy that merits further exploration.