槐果碱通过HTR3A抑制骨肉瘤细胞增殖OA

Objective To analyze and verify the mechanism of sophocarpine in inhibiting os-teosarcoma cells through network pharmacology and in vivo and in vitro experiments.Methods The targets of sophocarpine were predicted by network pharmacology.The relationship between 5-hydroxytryptamine receptor 3A(HTR3A)and prognosis of osteosarcoma was analyzed by bioinfor-matics.HTR3A was knocked down in osteosarcoma cell lines U2OS and MG63,and its effects on cell proliferation,colony formation,apoptosis,and the expression levles of cell cycle-related pro-teins were detected.The inhibitory effects of sophocarpine on the growth of osteosarcoma cells and transplanted tumors were observed by in vitro and in vivo experiments.Results HTR3A was predic-ted as a key target of sophocarpine,and its high expression level was associated with poor prognosis in patients with osteosarcoma(log-rank P<0.05,P<0.05).HTR3A was highly expressed in os-teosarcoma cells,and knockdown of HTR3A inhibited cell proliferation and colony formation,and induced cell cycle arrest and apoptosis(P<0.05).Sophocarpine effectively inhibited the growth of osteosarcoma in vitro and in vivo(P<0.05),and the HTR3A protein expression level was de-creased after sophocarpine treatment in a dose-dependent manner(P<0.05).Moreover,overex-pression of HTR3A reversed the inhibitory effect of sophocarpine on cell proliferation(P<0.05).Conclusion Sophocarpine can inhibit the proliferation and colony formation and promote apoptosis of osteosarcoma cells by inhibiting the expression of HTR3A.HTR3A is a potential key target for so-phocarpine to exert anti-tumor effect in osteosarcoma.