Therapeutic targeting of Bmi1 with PTC-209 in tongue squamous cell carcinoma in vitro
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摘要:
目的：检测Bmi1（B lymphoma Mo-MLV insertion region 1）小分子化学抑制剂PTC-209对人舌鳞癌细胞中Bmi1表达的抑制作用，并探讨其对体外人舌鳞癌细胞生物表型的影响。方法：对人舌鳞癌细胞系Cal27予以PTC-209处理，通过蛋白质免疫印迹、实时定量逆转录聚合酶链反应检测PTC-209干预后细胞内Bmi1的表达变化；通过MTT、Transwell、划痕试验等分析PTC-209处理对人舌鳞癌细胞增殖、迁移和侵袭的影响；应用克隆形成、肿瘤球培养、流式分选等实验分析PTC-209对人舌鳞癌细胞系中肿瘤干细胞亚群的影响。结果：PTC-209能显著下调人舌鳞癌细胞中Bmi1的表达，并具有浓度和时间依赖效应（P＜0.05）；PTC-209体外干预可明显抑制细胞增殖、侵袭和迁移能力，增强细胞对顺铂和5-FU的药物敏感性；PTC-209能显著降低细胞克隆形成率、肿瘤球形成以及ALDH+亚群细胞比例。结论：PTC-209能在体外抑制人舌鳞癌细胞中Bmi1的表达，具有抑制细胞增殖、侵袭迁移和降低肿瘤干细胞亚群比例等抗肿瘤效应。
Abstract:
Objective：In the present study，we aimed to investigate the small-molecule B lymphoma Mo-MLV insertion region 1 (Bmi1) inhibitor，PTC-209，for its effects on endogenous Bmi1 expression and cell behaviors in tongue squamous cell carcinoma (TSCC) cell line in vitro. Methods：The TSCC cell line Cal27 was treated with PTC-209 in vitro，and the expression change of Bmi1 was detected by Western blotting and real-time RT-PCR assays. The changes of cell proliferation，invasion and migration were analyzed by MTT，transwell and wound-healing assay，respectivety. The cancer stem cell (CSC) subpopulations in Cal27 were further assayed by tumorsphere formation，colony-forming and flow cytometry assays. Results：Bmi1 mRNA and protein levels were significantly decreased in Cal27 cells treated with PTC-209 in both dose- and time-dependent manners (P＜0.05). PTC-209 inhibited cell proliferation，migration and invasion，and had synergic anti-cancer effects when combined with cisplatin and 5-FU. Moreover，colony formation，sphere formation，and ALDH+ subpopulation were significantly reduced upon PTC-209 exposure. Conclusion：PTC-209 treatment induces Bmi1 reduction in TSCC cell line in vitro，and shows potent anti-tumor activity with reduced cell proliferation，migration，invasion and CSC subpopulation.
