Effect And Mechanism Of High Glucose On MICA/B Of Pancreatic Cancer Cells

Objective: Pancreatic cancer was closely related to diabetes.The mortality of pancreatic cancer patients with diabetes mellitus was significantly higher than the patients without diabetes mellitus,but the specific mechanisms have not been studied clearly.This study investigated the killing effects of NK-92 cells to pancreatic cancer cell lines treated after high glucose and the effects of high glucose treatment on Bmi1,MICA/B and GATA2 proteins in pancreatic cancer cells,and explored the mechanism of inhibited MICA/B expression and immune killing process induced by high glucose.Methods: The cytotoxicity of NK-92 cells to pancreatic cancer cells treated with high glucose was detected by lactate dehydrogenase release assay.The expression changes of MICA/B after high glucose treatment were detected by qRT-PCR,Western Blot and flow cytometry;The expression of Bmi1 after high glucose treatment were detected by qRT-PCR,Western-Blot and immunofluorescence techniques;The overexpression plasmid and SiRNA transfection techniques were used to further verify the role of Bmi1 and GATA2 in suppressing MICA/B expression induced by high glucose.Results: High glucose could inhibit the cytotoxicity of NK-92 cells to pancreatic cancer cells by inhibiting the expression of MICA/B;High glucose could promote the expression of Bmi1,at the same time,overexpression of Bmi1 could inhibit the expression of MICA/B,reduce the killing effect of NK-92 cells and promote the expression of GATA2.GATA2 knockdown could promote the expression of MICA/B in pancreatic cancer cells.Conclusion: High glucose could decrease the immune killing effect of NK-92 cells through reducing the expression of MICA/B in pancreatic cancer cells.Bmi1 and GATA2 proteins played an important role in the immune escape of pancreatic cancer cells to NK-92 cells induced by high glucose.