DGAT1 Suppresses Pancreatic Cancer Cell Ferroptosis And Mediates Radiotherapy Tolerance By Promoting Lipid Droplet Formation

Purpose: Pancreatic cancer is a malignant tumor with extremely poor prognosis.At present,surgical treatment is the main treatment.However,most patients with pancreatic cancer lose the chance of surgery due to late detection.Therefore,radiotherapy is one of the main treatment methods for advanced patients,playing an important role in treatment.However,radiotherapy resistance is often the main cause of pancreatic cancer treatment failure,and the mechanism of pancreatic cancer radiotherapy resistance formation is complex.Current studies have shown that the reprogramming of lipid metabolism in pancreatic cancer is related to the occurrence and development of pancreatic cancer,among which DGAT1 is a lipid droplet-associated protein that plays an important role in the occurrence and development of various tumors,but DGAT1 is related to the radiotherapy resistance of pancreatic cancer Sexual research is scarce.This study aims to explore DGAT1 inhibiting pancreatic cancer cell ferroptosis by promoting lipid droplet formation and mediating radiotherapy resistance(the effect on the radiosensitivity of pancreatic cancer cells and its regulatory mechanism),and to provide a new theory for radiosensitization of pancreatic cancer base and target.Methods: 1.Ualcan,GEPIA,and HPA online databases were used to analyze the expression difference of DGAT1 in pancreatic cancer tissues and normal tissues.2.Extract the RNA of KPC cells before and after radiotherapy and send it to Novogene for detection,and obtain relevant RNA sequencing results.3.The expression level of DGAT1 protein in KPC cells before and after radiotherapy was detected by Western blotting.4.The effect of DGAT1 on lipid droplets in KPC cells after radiotherapy was detected by laser confocal and flow cytometry.5.The effect of DGAT1 on the level of ferroptosis in KPC cells after radiotherapy was detected by MDA kit and flow cytometry.6.The effect of DGAT1 on the proliferation of KPC cells after radiotherapy and related mechanisms were detected by CCK-8 kit and plate colony formation assay.Results:Ualcan,GEPIA,and HPA databases showed that the expression of DGAT1 in pancreatic cancer tissues was up-regulated compared with normal tissues.The results of RNA sequencing showed that there were significant differences in the transcriptional profiles of KPC cells before and after radiotherapy,and the lipid metabolism pathways in KPC cells after radiotherapy were significantly enriched by KEGG pathway analysis.The results of Western blotting showed that the protein level of DGAT1 in KPC cells increased after radiotherapy.The results of laser confocal and flow cytometry experiments showed that DGAT1 promoted the formation of lipid droplets in KPC cells after radiotherapy.MDA kit,and flow cytometry detection results showed that DGAT1 induced a decrease in the level of ferroptosis in KPC cells after radiotherapy.The results of CCK-8 kit detection and plate colony formation experiments showed that DGAT1 promoted the proliferation and colony formation of KPC cells after radiotherapy,and the mechanism may be related to ferroptosis.Conclusions: The expression of DGAT1 in pancreatic cancer cells increases after radiotherapy.DGAT1 promotes the formation of lipid droplets in pancreatic cancer cells after radiotherapy and promotes the proliferation and clone formation of KPC cells after radiotherapy,thereby mediating radiotherapy resistance.Mechanistically,DGAT1 may reduce radiosensitivity by inhibiting ferroptosis in pancreatic cancer.