Study On The Role Of Lactate-monocarboxylate Transporter 1 In The Proliferation,Migration And Invasion Of Pancreatic Cancer

Purposes This study aims to investigate the effects of lactate on the biological function of pancreatic cancer in different microenvironment,and to further study the role and molecular mechanism of lactate-MCT1 axis in it,which may provide new directions and ideas for the comprehensive treatment of pancreatic cancer.Methods DMEM medium and sugar-free medium were used to simulate normal glucose microenvironment and low glucose microenvironment in vitro,and then additional lactate of 5m M,10 m M,20 m M were added in the above two media.MTT cell proliferation assays and clone formation assays were used to detect the proliferation ability of pancreatic cancer cells.wound-healing assays and transwell invasion assays were used to detect the migration and invasion ability of pancreatic cancer cells.Then,RNAi technique was used to knockdown the expression of MCT1 in pancreatic cancer cells,and the knockdown efficiency was detected by q RT-PCR and Western Blot assays.Secondly,the biological changes of proliferation,migration and invasion of pancreatic cancer cells after knocking down MCT1 were detected under the condition of normal glucose + lactate and low glucose + lactate.To explore whether the biological effect of pancreatic cancer cells induced by lactate in low glucose microenvironment depends on MCT1.Finally,the expression of MCT1 in pancreatic cancer and its relationship with survival and prognosis were analyzed by bioinformatics method.Results In our study,we found that a certain concentration of lactate(10m M)can promote the proliferation,migration and invasion of pancreatic cancer cells under low glucose microenvironment.But in the normal glucose microenvironment,these effects disappear.After the expression of MCT1 in pancreatic cancer cell line was knocked down by RNAi technique,the proliferation,migration and invasion ability of pancreatic cancer cells induced by lactic acid under glucose deprivation were significantly decreased.Under normal glucose microenvironment,knocking down MCT1 did not affect the proliferation,migration and invasion of pancreatic cancer cells.Finally,Through bioinformatics analysis,it was found that MCT1 was highly expressed in pancreatic cancer,and its high expression was related to the poor prognosis of patients with pancreatic cancer.Moreover,the expression of MCT1 in patients with high stage pancreatic cancer is also increased,suggesting the role of MCT1 in promoting pancreatic cancer.Conclusions Lactate under normal glucose had no obvious effect on proliferation,migration and invasion of pancreatic cancer cells.Under the condition of low glucose,10 m M lactate can maintain the survival of pancreatic cancer cells and promote their migration and invasion ability.The effect reached the maximum at 20 m M lactate and the effect of lactate was MCT1-dependent.These results suggest that lactate-MCT1 axis plays an important role in pancreatic cancer,but the molecule mechanism of lactate-MCT1 is still needed to be further studied.