AR-A014418抑制SOX2的表达促进软骨肉瘤顺铂敏感

AR-A014418 inhibits the expression of SOX2 and promotes the sensitivity of chondrosarcoma to cisplatin

目的:通过细胞实验探究GSK3β基因对人类软骨肉瘤细胞系HCS 2/8和SW 1353的影响。方法:细胞计数试剂盒8(CCK-8)和克隆形成实验检测细胞的增殖能力;Transwell实验检测软骨肉瘤(CS)细胞的侵袭能力;划痕实验检测CS细胞的迁移能力;蛋白质印迹法(Western blot)检测细胞内SOX2蛋白变化;通过联药实验验证AR-A014418和顺铂联合用药的效果。结果:敲低GSK3β显著抑制软骨肉瘤增殖和侵袭能力(P<0.05)。Western blot实验发现随着GSK3β敲低,细胞内SOX2的蛋白表达量下降(P<0.05),并且其mRNA水平没有显著变化(P>0.05)。AR-A014418可以有效抑制CS细胞内SOX2的表达,AR和顺铂联合用药效果显著。结论:敲低GSK3β能够抑制SOX2的蛋白表达而促进CS对化疗的敏感性。AR-A014418作为GSK3β的特异性抑制剂,具有杀伤CS细胞的作用,其能与顺铂有良好的联药效果。

Objective:To investigate the effect of GSK3βgene on human chondrosarcoma cell lines HCS 2/8 and SW 1353 by cell experiments.Methods:CCK-8 and colony formation assay were used to detect cell proliferation ability;Transwell assay was used to detect cell invasion ability;wound-healing assay was used to detect cell migration ability;Western blot was used to detect changes of SOX2 in cells;combination experiments were made to verify the effect of AR-A014418 combined with cisplatin.Results:Knockdown of GSK3βsignificantly inhibited the proliferation and invasion ability of chondrosarcoma(P<0.05).With GSK3βknockdown,the protein expression of SOX2 in cells decreased(P<0.05),and its mRNA level did not change significantly(P>0.05).AR-A014418 could effectively inhibit the expression of SOX2 in CS cells,and the combination of AR and cisplatin produced significant effect.Conclusion:Knockdown of GSK3βcan inhibit the protein expression of SOX2 and promote the sensitivity of chondrosarcoma to chemotherapy.As a specific inhibitor of GSK3β,AR-A014418 has the function of killing chondrosarcoma cells,which has good combination effect with cisplatin.