摘要
Lanthanum ions （La3＋） have been reported to exert profound effects on the proliferation of NIH 3T3 mouse embryonic fibroblasts. In the present studies, the pro-proliferative effect of La3＋ on NIH 3T3 cells was further characterized, and its impacts on the cell cycle kinetics were analyzed in detail by cell cycle arrest-and-release and pulse BrdU-labeling and chasing experiments. The results show that La3＋ promoted the proliferation of NIH 3T3 cells after 12 h and the ECs0 was 2.4 ktM after 48 h. Such effect was also confirmed by enhanced BrdU incorporation. La3＋ stimulated more cells to pass through the G1/S checkpoint into S phase, but did not change the length of cell cycle. Furthermore, La3＋-treatment increased the protein levels and nuclear localization of cyclin D 1 and c-Myc, two key regulators of G1/S checkpoint, as demonstrated by immunostaining. The pro-proliferative effects of La3＋ share striking similarity with that of Gd3＋, and provided new information regarding the cellular biological activities of lanthanides.
镧离子(La3+)对NIH 3T3小鼠胚胎成纤维细胞的增殖有重要影响,但其机理尚需深入研究。在本研究中,我们运用增殖分析、周期阻滞-释放和BrdU追踪等方法详细分析了La3+对NIH 3T3细胞增殖及细胞周期动力学的影响。结果显示,La3+处理12小时即有显著促增殖作用,在48小时促增殖效应的EC50为2.4μM。La3+促NIH 3T3细胞增殖的作用也在BrdU掺入实验中得到了验证。La3+推动更多细胞跨过G1/S周期检查点进入S期,但不改变细胞周期的时间长度。免疫荧光染色发现,La3+处理增加了两个关键细胞周期调控因子cyclin D1和c-Myc的蛋白水平和细胞核定位。本研究显示La3+的促增殖作用与报道的可能引起肾源性系统性纤维化疾病的Gd3+非常相似,并提供了镧系元素细胞生物学活性的新信息。
基金
National Natural Science Foundation (Grant No.21001011)
Key Program of National Natural Science Foundation of China (Grant No. 41130746)
