[关键词]
[摘要]
目的:探讨1,25-二羟维生素D3 [1,25(OH)2D3]对食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)细胞增 殖、迁移和细胞周期的影响及其相关机制。方法:用不同浓度1,25(OH)2D3处理ESCC细胞TE-11、KYSE30、TE-1和KYSE510后, 用CCK-8法检测细胞的增殖能力。再用浓度分别是0、0.1、0.15、0.2 μmol/L的1,25(OH)2D3处理TE-11和KYSE30细胞,划痕愈合 实验、流式细胞术分别检测细胞的迁移能力和细胞周期分布情况,WB法检测细胞中cyclin D1、P27、ERK和p-ERK蛋白的表达水 平。结果:1,25(OH)2D3 显 著 抑 制 TE-11 和 KYSE30 细 胞 的 增 殖 能 力 ,其 抑 制 程 度呈时间依赖性和浓度依赖性。0.1和 0.2 μmol/L的1,25(OH)2D3处理48 h后,与空白对照组比较,TE-11和KYSE30细胞的迁移能力均显著降低(P<0.05或P<0.01),处 于G0/G1期细胞显著增加(P<0.05或P<0.01),细胞中 cyclin D1 和 p-ERK 蛋白水平显著下调、P27 蛋白水平明显上调(P<0.05或P<0.01)而ERK蛋白的表达无明显变化。结论:1,25(OH)2D3显著抑制ESCC细胞的增殖和迁移能力并阻滞细胞周期进程,其 可能通过调控ERK信号通路而发挥作用。
[Key word]
[Abstract]
Objective: To investigate the effects of 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) on the proliferation, migration and cell cycle of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: Human ESCC cells (TE-1, KYSE30, TE-11 and KYSE510) were treated with different concentrations of 1,25(OH)2D3, and the proliferation was detected by CCK-8. TE-11 and KYSE30 cells were treated with 1,25(OH)2D3 at concentrations of 0, 0.1, 0.15, and 0.2 μmol/L, respectively. Scratch healing test was used to detect cell migration ability, Flow cytometry was used to detect cell cycle distribution, and WB was used to detect the protein expressions of cyclin D1, P27, ERK and p-ERK. Results: 1,25(OH)2D3 significantly inhibited the proliferation of TE-11, KYSE30 cells in a concentration- and time-dependent manner (P<0.05 or P<0.01). As compared with control group, TE-11 and KYSE30 cells that treated with 0.1 and 0.2 μmol/L 1,25(OH)2D3 for 48 h exhibited significantly inhibited migration ability (P<0.05 or P<0.01),increased cell population at G0/G1 phase (P<0.05 or P<0.01),decreased protein expressions of cyclin D1 and p-ERK (P<0.05 or P<0.01),and increased expression of P27 protein (P<0.05 or P<0.01);however, there was no significant difference in total ERK level. Conclusion: 1,25(OH)2D3 can significantly inhibit the proliferation, migration and block the cell cycle of ESCC cells, which may be through the regulation of ERK signal pathway.
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[基金项目]
四川省科技创新苗子工程培育项目(No.2020104);四川省科技计划项目(No.2018SZ0377, No.2018JY0219);南充市市校合作科研 专项资金(No.18SXHZ0208, No.18SXHZ0366, No.18SXHZ0381)