一贯煎影响肝癌干细胞抑制肝细胞癌的作用机制研究OA

Objective To investigate the mechanism of action of Yiguanjian Decoction(YGJ)and its constituents in regulating hepatocellular carcinoma(HCC)by affecting liver cancer stem cells(LCSCs)through lysyl-oxidase like-2(LOXL2).Methods CD133+LCSCs were sorted and constructed to down-regulate LOXL2,cellular experiments were performed,and YGJ intervened to silence LOXL2 LCSCs.Through network pharmacology screening,the primary active components of YGJ were identified as quercetin and isoflavone.Both quercetin and isoflavone belong to the dihydroflavone class and share structural similarities.It has been established that isoflavone inhibits the proliferation of HCC.Inhibition of LCSC Proliferation by Quercetin as Detected by the CCK-8 Assay.Construction of LOXL2 and its downstream factors proto-oncogene tyrosine-protein kinase SRC,phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3CA)LCSCs were transfected with the overexpression plasmid of PIK3CA.Dual luciferase reporter assay was performed to detect the regulation of LOXL2 and SRC,PIK3CA by quercetin.Establishment of subcutaneous grafted tumor model in nude mice with LCSCs and validation of the effects of LOXL2,SRC,and PIK3CA on HCC in tumor tissues of nude mice in each group after drug intervention.Results Knockdown of LOXL2 inhibited the proliferation,invasion,and migration of LCSCs.YGJ affected LOXL2 expression to inhibit the proliferation and promote apoptosis of LCSCs.Quercetin inhibited the proliferation of LCSCs by down-regulating the expression of LOXL2 and downstream factors SRC and PIK3CA genes,and further inhibited the growth of LCSCs implantation tumors in nude mice in vivo.Conclusion YGJ and quercetin affect LCSCs by down-regulating LOXL2 and its downstream SRC and PIK3CA genes to further inhibit HCC progression.