Abstract：
The study investigates the anticancer activity of mefenamic acid against osteosarcoma, shedding light on its underlying mechanisms and therapeutic potential. Mefenamic acid exhibited robust inhibitory effects on the proliferation of MG-63, HOS, and H2OS osteosarcoma cells in a dose-dependent manner. Moreover, mefenamic acid induced cellular toxicity in MG63 cells, as evidenced by LDH leakage, reflecting its cytotoxic impact. Furthermore, mefenamic acid effectively suppressed the migration and invasion of MG-63 cells. Mechanistically, mefenamic acid induced apoptosis in MG-63 cells through mitochondrial depolarization, activation of caspase-dependent pathways, and modulation of the Bcl-2/Bax axis. Additionally, mefenamic acid promoted autophagy and inhibited the PI3K/Akt/mTOR pathway, further contributing to its antitumor effects. The molecular docking studies provide compelling evidence that mefenamic acid interacts specifically and strongly with key proteins in the PI3K/AKT/mTOR pathway, suggesting a novel mechanism by which mefenamic acid could exert anti-osteosarcoma effects. In vivo studies using a xenograft mouse model demonstrated significant inhibition of MG-63 tumor growth without adverse effects, supporting the translational potential of mefenamic acid as a safe and effective therapeutic agent against osteosarcoma. Immunohistochemistry staining corroborated the in vivo findings, highlighting mefenamic acid\'s ability to suppress tumor proliferation and inhibit the PI3K/AKT/mTOR pathway within the tumor microenvironment. Collectively, these results underscore the promising therapeutic implications of mefenamic acid in combating osteosarcoma, warranting further investigation for clinical translation and development.
摘要：
该研究调查了甲芬那酸对骨肉瘤的抗癌活性，揭示其潜在的机制和治疗潜力。甲芬那酸对MG-63、HOS、和H2OS骨肉瘤细胞呈剂量依赖性。此外，甲芬那酸诱导MG63细胞的细胞毒性，LDH泄漏证明，反映了它的细胞毒性影响。此外，甲芬那酸可有效抑制MG-63细胞的迁移和侵袭。机械上,甲芬那酸通过线粒体去极化诱导MG-63细胞凋亡,caspase依赖性途径的激活，和Bcl-2/Bax轴的调制。此外,甲芬那酸促进自噬并抑制PI3K/Akt/mTOR通路,进一步促进其抗肿瘤作用。分子对接研究提供了令人信服的证据，证明甲芬那酸与PI3K/AKT/mTOR通路中的关键蛋白特异性和强烈地相互作用，提示甲芬那酸可以发挥抗骨肉瘤作用的新机制。使用异种移植小鼠模型的体内研究表明，对MG-63肿瘤生长有显著的抑制作用，而没有不良反应。支持甲芬那酸作为一种安全有效的骨肉瘤治疗剂的翻译潜力。免疫组织化学染色证实了体内发现，强调甲芬那酸在肿瘤微环境中抑制肿瘤增殖和抑制PI3K/AKT/mTOR通路的能力。总的来说，这些结果强调了甲芬那酸在对抗骨肉瘤中的有希望的治疗意义，保证进一步调查临床翻译和开发。
