The Role Of ILK And Its Mechanism Of Glucose Metabolism In Human Gastric Cancer Cell Lines

Objective: To explore the effects and mechanisms of ILK on the proliferation and invasion of gastric cancer cells by regulating the glucose metabolism of tumor cells.Methods: We stimulated the gastric cancer cells with the ILK small molecule inhibitor,Cpd22,and the inhibitory effect on the proliferation and invasion of gastric cancer cells was detected.The metabolism analyzer machine(Seahorse)was used to observe the changes of oxidative phosphorylation and glycolysis levels after gastric cancer cells were stimulated by inhibitors;To explore the mechanism of this change,we use CRISPR/Cas9 to construct ILK completely knock-out gastric cancer cell lines,then we detect proliferation,invasion and metabolism,and find the corresponding mechanism changes by detecting downstream genes and proteins.Results: We found that ILK inhibitor inhibited the function of ILK in gastric cancer cells,and the ability of gastric cancer cells to proliferate and invade were significantly reduced as well.Furthermore,the oxidative phosphorylation and glycolysis of gastric cancer cells were also reduced,and simultaneously reducing cell lactic acid production and ROS levels.Inhibiting ILK in gastric cancer cells affects the production of IL-6 and inhibits the STAT3,PKB/Akt,and GSK3β signaling pathways.The established knockout cell lines further verified the above results.Conclusion: ILK promoted the proliferation and invasion of gastric cancer cells.ILK also enhanced glycolysis and oxidative phosphorylation and increase the level of IL-6 through STAT3、PKB/Akt、GSK3β signaling pathways in human gastric cancer.Small molecule inhibitors can effectively inhibit the function of ILK protein in gastric cancer cell lines and provided a new target and direction for the selection of new tumor markers and targeted therapeutic approach for gastric cancer.