Effect And Mechanism Of Curcumol On Expression Of PD-L1 In Hepatocellular Carcinoma Cell

Aim of the study:Curcumol is derived from the dried rhizome of Curcuma wenyujin Y.H.Chen et C.Ling,which has anti-oxidation,anti-virus,antibacterial anti-inflammatory and anti-tumor effects.However,the molecular mechanism of curcumol on anticancer have not been fully elucidated.This article mainly studied the effect of curcumol on the expression of programmed cell death ligand 1(PD-L1)in hepatocellular carcinoma and determined its mechanism.Methods:The effects of curcumol on the binding mode of STAT3 or HIF-1α,transcription activity and cell viability were detected by molecular docking experiment,luciferase reporter gene assay and MTT assay;The effects of curcumol on the expression and location of STAT3,HIF-1α or PD-L1 protein were studied by RT-PCR,Western blot and immunofluorescence;EdU-labeled immunofluorescence method,colony formation,flow cytometry,scratch,transwell assays,tube formation and T cell killing experiments were used to explore the effects of curcumol on cell proliferation,angiogenesis and tumor killing activity on hepatocellular carcinoma cells;In vivo,the effects of curcumol on hepatocellular carcinoma cells were evaluated in xenograft tumor model and immunohistochemical experiments.Results:According to the results of molecular docking experiment,curcumol had a good binding effect with STAT3 or HIF-1α.The luciferase reporter gene and MTT experiments detected that the inhibitions of STAT3 and HIF-1α transcriptional activation were not correlated with curcumol induced cytotoxicity.Western blot experiment showed that curcumol reduced the expression of p-STAT3(Tyr705)by regulating JAK1,JAK2 and Src pathways,and inhibited the protein synthesis of HIF-1α by regulating mTOR/p70S6K/4E-BP1/eIF4E and MAPKs pathway.It was also found that curcumol inhibited the expression of PD-L1 at the mRNA and protein expression by inhibiting the interaction between STAT3 and HIF-1α.In addition,by inhibiting the expression of PD-L1,curcumol could inhibit the proliferation of tumor cells,the angiogenesis,metastasis and invasion of endothelial cells and could restore the activity of cytotoxic T cells and their ability to kill tumor cells.In vivo experiment confirmed that curcumol could inhibit tumor growth in the xenograft tumor modelConclusion:Curcumol inhibited the expression of PD-L1 in hepatocellular carcinoma cell by inhibiting the interaction between HIF-1α and STAT3 signaling pathways and thereby inhibited the occurrence and development of tumor.The research results provided a theoretical basis for the further development of curcumol.