Ezetimibe inhibits cell viability and invasion by suppressing PI3K/AKT signaling pathway in human osteosarcoma cells

Qiuyan Weng, Jianning Luo, Yong Zhang, Tongzhou Hu
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Abstract

Osteosarcoma is one of the most prevalent malignant bone tumors with a poor overall prognosis and mainly happens in children and adolescents. Current therapy strategies still possess a lot of limitations, and new and efficient strategies are required. Ezetimibe was previously reported to have its anti-tumor effect in various tumors, but the investigation of Ezetimibe on osteosarcoma is still limited. This study explores whether ezetimibe could exert an anti-tumor effect on human osteosarcoma cell lines, U2OS, and Saos-2. The effect of ezetimibe on the proliferation of osteosarcoma was explored by CCK-8 and colony formation assay. The role of ezetimibe on osteosarcoma cell migration and invasion was explored by wound healing assay and transwell assay. The role of ezetimibe on osteosarcoma cell apoptosis was explored by PI/Annexin V analysis. In addition, a western blot was performed to verify the phenotype. The flow cytometry assay indicated that ezetimibe could promote osteosarcoma apoptosis. Western blot assay further demonstrated the effect of ezetimibe on proliferation, migration, invasion and apoptosis-related proteins. Finally, the deep anti-tumor effect of ezetimibe contributed to suppressing the PI3K/AKT signaling pathway. Present data indicated that ezetimibe has an antitumor effect on osteosarcoma and could be considered a future osteosarcoma treatment.
依折替米贝通过抑制人骨肉瘤细胞PI3K/AKT信号通路抑制细胞活力和侵袭
骨肉瘤是最常见的恶性骨肿瘤之一,总体预后较差,多见于儿童和青少年。目前的治疗策略仍有很多局限性,需要新的有效的治疗策略。Ezetimibe在多种肿瘤中均有抗肿瘤作用,但对Ezetimibe对骨肉瘤的研究仍然有限。本研究探讨依zetimibe是否能对人骨肉瘤细胞系U2OS和Saos-2发挥抗肿瘤作用。通过CCK-8和集落形成实验探讨依折替米比对骨肉瘤增殖的影响。通过伤口愈合实验和transwell实验探讨依折替米布对骨肉瘤细胞迁移和侵袭的作用。通过PI/Annexin V分析,探讨依折替米对骨肉瘤细胞凋亡的作用。此外,进行western blot验证表型。流式细胞术检测表明依折替米贝能促进骨肉瘤细胞凋亡。Western blot进一步证实依折替米贝对细胞增殖、迁移、侵袭和凋亡相关蛋白的影响。最后,依zetimibe的深层抗肿瘤作用有助于抑制PI3K/AKT信号通路。目前的数据表明依折替米比对骨肉瘤有抗肿瘤作用,可以考虑将来治疗骨肉瘤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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