益智仁中的喇叭茶醇通过降低肝细胞癌中PD-L1表达增强抗PD-1药物的联合药理作用

Introduction: Globulol is a terpenoid metabolite isolated from Alpinia oxyphylla Miq. Previous studies have demonstrated that terpenoid metabolites exhibit anti-inflammatory, antioxidant, and antitumor activities. However, the exact mechanisms by which Globulol impacts HCC remain obscure.Materials and Methods: The influence of Globulol on HCC cell lines was assessed in vitro employing the CCK8, EdU cell proliferation assays, a three-dimensional tumor spheroid model, and flow cytometry. The combination effects of Globulol and anti-PD-1 was explored in an HCC and CD8+T cell co-culture model. The molecular pathways influenced by Globulol in HCC were delineated through transcriptomic sequencing, molecular docking, bioinformatics approach, cell transfection, quantitative reverse transcription-PCR, and Western blot analysis.Results: Globulol notably decreased the viability of Huh1/Huh7 cells in a concentration-dependent manner. It was found to prompt the secretion of the chemokine CCL4 by tumor cells, enhancing the infiltration of cytotoxic CD8+T cells into the HCC microenvironment. Further research has indicated that globulol inhibits PD-L1 expression by targeting the PAK4-pAKT-STAT3 axis, improves the immunosuppressive microenvironment of HCC, and enhances the pharmacological effects in combination with Tislelizumab.Conclusion: These results suggest that Globulol can promote a microenvironment permissive to PD-1 blockade, thereby exerting anti-HCC activity. Hence, the combination of Globulol and PD-1 blockade may be a promising strategy for HCC treatment.