Effects Of Pancreatic Cancer Cell Soluble Secretions On Lipid Metabolism In Mice

Background & Objective Cancer cachexia is a kind of metabolic syndrome caused by malignant tumors.Pancreatic cancer patients have a very high incidence of cancer cachexia,and researchers have conducted a large number of studies on it.No complete pathogenesis of cancer cachexia has been discovered so far.Fat metabolism is extremely important in the metabolic disorder of cancer cachexia.The decomposition of fat in patients with cancer cachexia increases and the adipose tissue is consumed in a large amount.Lipid production is blocked,and fatty acid oxidation is strengthened,resulting in a decrease in fat storage.A number of studies have shown that tumor cells can secrete several cytokines,which can cause an imbalance in lipid metabolism.However,it is difficult to observe the effects of tumor tissue secretion on adipose tissue.In this study,BALB/c mice were injected with conditioned medium of pancreatic cancer cells.A total of two sub-studies were conducted.In the first study,mice were injected with three pancreatic cancer cell lines(Panc-1,MiaPaCa-2,BxPC-3)conditioned medium to observe the changes in lipid metabolism induced by soluble secretion from pancreatic cancer cells.The second study only involved conditioned medium from MiaPaCa-2 cells and investigated the effect of different doses of tumor secretion on lipid metabolism.Methods The conditioned medium of pancreatic cancer cells was the supernatant obtained from serum-free medium culturing pancreatic cancer cells for 24 h.The whole experiment included 2 sub-studies,in the first one,the condition medium of 3 pancreatic cancer cell lines(Panc-1,MiaPaCa-2,BxPC-3)and normal DMEM were injected into mice in different groups.The mice in each group received subcutaneous injection twice a day for 7 days.Body weight and food intake of each mouse was recorded.Insulin,glucose and triglyceride contents in plasma were detected.Pancreas and liver were weighed,and hepatic glycogen and muscle glycogen were detected.Inguinal fat depots and epididymal fat depots were weighed.The expression levels of adipose triglyeride lipase protein were detected.In the second sub-study,the different doses of MiaPaCa-2 cell conditioned medium were injected into the corresponding groups of mice,the rest was consistent with the former sub-study.Results In the first sub-study,the food intake and body weight of the four groups of mice decreased at the initial stage.Compared with the control group injected with normal DMEM,significant insulin resistance occurred in mice injected with conditioned media of MiaPaCa-2 and BxPC-3 pancreatic cancer cells.The insulin resistance was shown an increase in plasma insulin,plasma glucose levels,and decrease in hepatic glycogen contents.Moreover,all the groups injected with conditioned medium of pancreatic cancer cells showed a significant decrease in the expression level of ATGL protein,suggesting a decrease in lipolysis.A decrease in plasma triglyceride content and an increase in fat storage were also observed.In the second experiment,the plasma insulin and glucose levels were elevated.The hepatic glycogen decreased in the two groups injected with different doses of pancreatic cancer cell conditioned medium,and the high dose group had statistical differences,which proved that high doses of injection can cause greater insulin resistance.In addition,the lipid metabolism in the two groups of mice injected with pancreatic cancer cells conditioned medium showed a weakening trend,and the high dose group was more effective than the low dose group.Conclusion The above results indicate that injection of conditioned medium of pancreatic cancer cells into mice can cause imbalance of fat metabolism and insulin resistance,and decrease lipolysis.And the efficacy of different doses is different,the imbalance of fat metabolism is more obvious in the high-dose injection group,the insulin resistance is more pronounced,the fat decomposition is weaker,and the storage is more.