Effects Of Cobalt Chloride On Gastric Carcinoma Cell SGC7901Proliferation And Apoptosis

Background and Objective The uncontrolled growth and exceeding energyconsumption lead to not only microenvironmental acidosis but also the change ofenergy production.Cancer cells generally exhibit increased glycolysis for ATPgeneration,the reason for abnormality of cancer cell metabolism and enhancementof glycolysis is quite complicated and maybe due in part to mitochondrial respirationinjury. Tumor cells use glucose as an energy source,increased glycolysis andbioenergetics may be the core of malignant transformation.Based on the geneexpression profiling established in the previous study of our lab, abnormalexpression shown in genes concerning cell proliferation, differentiation andappotosis as well as numerous differentially expressed genes associated withenergy metabolism have been identified.We analyzed the differentially expressedgenes involved in glycometabolism. In agreement with the increased glycolysis intumors, we found that hexokinase and pyruvate kinase was upregulated whilefructose-1,6-bisphosphatase(FBPase) was downregulated.As a result ofhexokinase II(HKII) expression had close relationship to gastric cancer,We selectedHKII for the further research.In order to further clarify the effects of hypoxia onenergy metabolism and biological function of tumor effects, we used cobalt chloride(CoCl2) treated SGC7901cells simulating gastric carcinoma in vivo hypoxiaenvironment,and observed HK II and HIF-1α expression in gastric cancer cellsunder hypoxic conditions, and observed the effects of hypoxia on gastric cancer cell,in order to explore the possible mechanism of adaptation to hypoxia in gastriccancer cells.Methods SGC7901cells were treated with50μm cocl2for24hours.theexpression levels of HKⅡand HIF-1α were detected by RT-PCR,Western Blot and immunofluorescence;and the change of cell apoptotic ratio were detected by flowcytometry;and the change of cell proliferation were detected by MTT.The content oflactic acid were detected by lactic acid determination reagent kit;ROS content weredetected by ROS determination reagent kit.Results Eexperimental results had shown that the hypoxia can significantlyincrease HKⅡ and HIF-1α mrna and the protein level of its expression in SGC7901treated by CoCl2.the hypoxia can enhance crowth of cell compared with controlclass, scratches healing assay indicated that migratory speed of the cell is stepup.these results shown that hypoxia can enhance malignancy reproductive activityof SGC7901.at the same time, lactate and ros content were increased,whichindicates the glycolytic pathway could be activate through high-expression of HKⅡand HIF-1α and mitochondrial injury.conclusion The hypoxia in SGC7901can enhance the malignantreproductive activity and invasion capability of cell. The abnormal expression of rosperhaps correlate with the decreased anti-oxidative ability and oxidation injury. Theoccurrence of ROS disrupting the respiratory chain may result in the disturbance ofenergy production. Simultaneously, the increased HKⅡ may increase glycolysis. Allthese events may closely associate with carcinogenesis and tumor development.Glycolysis enhancement induced lactic acid content increased, it will change cellsmicroenvironment of normal and tumor, normal cells may cause acidosis andapoptosis,but tumor cells growth is not affected by the adaptation mechanism, soglycolysis enhances may be one of the reasons of tumor metastasis andchemotherapy resistance.