The Role Of AKR1B10 On The Development Of Cholangiocarcinoma And The Underlying Mechanism

Background:Cholangiocarcinoma(CCA)is a bile duct malignancy arising from epithelial cells,also regarded as one of the most aggressive malignant cancers characterized by early local invasiveness and distant metastasis.AKR1B10 is a monomeric NADPH-dependent enzyme.It is highly expressed in many cancers and may facilitate the cell growth and proliferation via eliminating the high burden of carbonyl compounds.This study aimed to investigate the role of AKR1B10 on the development of CCA and the underlying mechanism.Methods:AKR1B10 expression was compared in 52 pairs of CCA patients,specimens using RT-PCR Western Blot and IHC.And the correlation between AKR1B10 expression and clinicopathological variables was analyzed.The effect of AKR1B10 on CCA cell proliferation,migration and invasion was detected both in vitro and in vivo.Flow cytometry was applied to detect CCA cell cycle.Western Blot was performed to detect some regulators in the proliferation-related signaling pathway.Results:AKR1B10 expression was significantly up-regulated in tumor tissues compared with adjacent non-tumor tissues in 52 paired CCA specimens.AKR1B10 increased the proliferation,migration and invasion abilities of CCA cells both in vitro and in vivo.Western Blot revealed that AKR1B10 significantly facilitated EMT process and activated the phosphorylation of Erk in CCA cells.Conclusion:AKR1B10 promotes the proliferation of CCA cells by activating the phosphorylation of Erk and increases the migration and invasion of CCA cells by accelerating EMT.