槐果碱通过HTR3A抑制骨肉瘤细胞增殖

doi:10.3870/j.issn.1672-8009.2026.01.008

摘要/Abstract

摘要： 目的基于网络药理学方法及实验室验证分析槐果碱对骨肉瘤细胞的作用机制。方法网络药理学预测槐果碱作用靶点;生物信息学分析5-羟色胺受体3A(HTR3A)与骨肉瘤预后的关系;在骨肉瘤细胞U2OS、MG63中敲低HTR3A,检测其对增殖、克隆、凋亡及细胞周期相关蛋白质的影响。观察槐果碱对骨肉瘤细胞及移植瘤生长的抑制作用,并验证HTR3A在其中作用。结果 HTR3A被预测为槐果碱的关键靶点,其高表达与骨肉瘤患者不良预后相关(log-rankP<0.05,P<0.05);在骨肉瘤细胞中HTR3A显著高表达,敲低HTR3A可抑制细胞增殖与克隆,诱导细胞周期阻滞与凋亡(P<0.05);槐果碱能呈浓度依赖性地下调HTR3A蛋白表达(P<0.05),并在体外和体内有效抑制骨肉瘤生长(P<0.05),过表达HTR3A则可逆转槐果碱对细胞增殖的抑制作用(P<0.05)。结论槐果碱可通过抑制HTR3A表达,进而抑制骨肉瘤细胞增殖、克隆并促进其凋亡。HTR3A是槐果碱发挥抗骨肉瘤作用的潜在关键靶点。

关键词: 槐果碱, 骨肉瘤细胞, 5-羟色胺受体3A, 细胞增殖, 网络药理学

Abstract: Objective To analyze and verify the mechanism of sophocarpine in inhibiting osteosarcoma 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 bioinformatics.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 proteins 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 predicted 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 osteosarcoma 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 decreased after sophocarpine treatment in a dose-dependent manner(P<0.05).Moreover,overexpression 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 sophocarpine to exert anti-tumor effect in osteosarcoma.

Key words: sophocarpine, osteosarcoma cells, 5-hydroxytryptamine receptor 3A, cell proliferation, network pharmacology

中图分类号:

R738.1

李霄雯, 赵洁, 江丽强, 张开, 贾海栋, 张存. 槐果碱通过HTR3A抑制骨肉瘤细胞增殖[J]. 医学分子生物学杂志, 2026, 23(1): 60-66.

LI Xiaowen, ZHAO Jie, JIANG Liqiang, ZHANG Kai, JIA Haidong, ZHANG Cun. Sophocarpine Inhibits Proliferation of Osteosarcoma Cells through HTR3A[J]. Journal of Medical Molecular Biology, 2026, 23(1): 60-66.

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