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氯化镧通过细胞周期机制促进NIH 3T3小鼠胚胎成纤维细胞增殖
  • 期刊名称:Journal of Chinese Pharmaceutical Sciences
  • 时间:2013.1.1
  • 页码:50-56
  • 分类:R96[医药卫生—药理学;医药卫生—药学]
  • 作者机构:[1]北京大学医学部药学院化学生物学系,北京100191, [2]西南科技大学环境与资源学院及固体废物处理与资源化教育部重点实验室,四川绵阳621010, [3]北京大学医学部医药卫生分析中心,北京100191
  • 相关基金:National Natural Science Foundation (Grant No.21001011); Key Program of National Natural Science Foundation of China (Grant No. 41130746)
  • 相关项目:重金属细胞毒性和致癌的化学预防:二甲苯酰甲烷及其衍生物的多靶机制
中文摘要:

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。

英文摘要:

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.

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