Effects Of Doxorubicin On Proliferation And Apoptosis Of Gastric Cancer BGC823 Cells Under Different PH Conditions And Preliminary Mechanism

BackgroundGastric cancer is one of the most common digestive tract tumors,and the mortality rate is the highest in the digestive tract tumors.Chemotherapy resistance of gastric cancer is the main cause of treatment failure in gastric cancer.There is an inextricable link between chemoresistance and the tumor microenvironment.Tumor microenvironment is a key factor in inducing cancer chemotherapy resistance.At present,there are few studies on the acid microenvironment and chemotherapy drug resistance of tumors at home and abroad.The aim of this study was to observe the effect of doxorubicin on the proliferation and apoptosis of gastric cancer BGC823 cells and the preliminary mechanism by adjusting the pH level in vitro.ObjectiveTo investigate the effects of doxorubicin on the proliferation and apoptosis of gastric cancer BGC823 cells under different pH conditions and the preliminary mechanism.MethodsThe effect of doxorubicin(ADM)cultured under different pH conditions on the proliferation of gastric cancer cell line BGC823 was detected by cell viability assay kit(CCK-8);Morphology of apoptotic cells were observed under fluorescence microscope;The apoptosis of BGC823 was assessed with Annexin V/PI;The expression of p-AKT,BCL-2 and NF-kB genes and proteins in gastric cancer cells were detected by qRT-PCR.Results1.The half-inhibitory concentration(IC50)of ADM on gastric cancer BGC823 cells was 5.277 ug/ml.Considering the toxicity of chemotherapy drugs and subsequent experiments,the ADM dose was selected to be 1/4 times the IC50 value of the cell line(1.32 ug/ml)for subsequent experiments;2.With the increase of pH,the inhibitory effect of ADM on the proliferation of BGC823 cells was enhanced.When the pH reached 7.4,the inhibition of proliferation was the most obvious.3.With the increase of pH,the apoptosis of BGC823 cells increased significantly with ADM.When the pH reached 7.4,the pro-apoptotic effect was the most obvious,and the pH concentration was further increased,and the ability to promote apoptosis was not obvious;4.Under different pH(pH 6.8~7.6)environment,the expression levels of Bcl-2,NF-κB and p-AKT genes decreased significantly with the increase of pH after ADM treatment.ConclusionIncreasing the extracellular pH can significantly increase the ability of ADM to inhibit cell proliferation and promote apoptosis in BGC823 cells.The anti-tumor effect of this pHrelated ADM may be achieved by inhibiting the phosphorylation of AKT and preventing the expression of anti-apoptotic proteins such as NF-κB and Bcl-2.