The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Cell Mol Biol (Noisy-le-grand). 2023 May 31;69(5):174-178. doi: 10.14715/cmb/2023.69.5.27.
C-Met receptor and its ligand hepatocyte growth factor (HGF) are overexpressed in a variety of osteosarcoma cell lines and osteosarcoma pathological samples. It is suggested that c-Met/HGF plays an important role in the development of osteosarcoma. This study aimed to explore the anticancer effect of the c-Met-targeted drug crizotinib on osteosarcoma (OS) cells. The effects of crizotinib on the proliferation of osteosarcoma cells (SaOS2, MG-63 and MNNG) at different concentrations were detected by CCK8. Human osteosarcoma cell line MG-63 was used as an in vitro model to evaluate the effects of 2.5 μM crizotinib, 5.0 μM crizotinib and DMSO on cell apoptosis, cell cycle, migration and invasion. The expression of the c-Met signaling pathway in osteosarcoma cells was detected by western blot. The results showed that crizotinib inhibited the proliferation of cell lines in a concentration-dependent manner. Crizotinib significantly increased the number of apoptotic cells compared with the control group. Compared with the control group, crizotinib increased G0/G1 phase cells and decreased S phase cells. Compared with the control group, crizotinib inhibited the migration and invasion of osteosarcoma cells and decreased the expression of c-Met/Gab1/STAT5. This study will provide a promising therapeutic target and theoretical basis for the clinical application of crizotinib in osteosarcoma.
C-Met 受体及其配体肝细胞生长因子 (HGF) 在多种骨肉瘤细胞系和骨肉瘤病理样本中过度表达。这表明 c-Met/HGF 在骨肉瘤的发生发展中起重要作用。本研究旨在探讨 c-Met 靶向药物克唑替尼对骨肉瘤（OS）细胞的抗癌作用。用 CCK8 检测不同浓度的克唑替尼对骨肉瘤细胞（SaOS2、MG-63 和 MNNG）增殖的影响。用人骨肉瘤细胞系 MG-63 作为体外模型，评估 2.5μM 克唑替尼、5.0μM 克唑替尼和 DMSO 对细胞凋亡、细胞周期、迁移和侵袭的影响。用 Western blot 检测骨肉瘤细胞中 c-Met 信号通路的表达。结果表明，克唑替尼呈浓度依赖性抑制细胞系的增殖。与对照组相比，克唑替尼显著增加了凋亡细胞的数量。与对照组相比，克唑替尼增加了 G0/G1 期细胞，减少了 S 期细胞。与对照组相比，克唑替尼抑制了骨肉瘤细胞的迁移和侵袭，并降低了 c-Met/Gab1/STAT5 的表达。本研究将为克唑替尼在骨肉瘤中的临床应用提供有前途的治疗靶点和理论基础。
