[1]王玲,余乐,古春萍,等.稳定表达Ras的人成纤维细胞改变自噬活性的细胞效应[J].南方医科大学学报,2014,(11):1578.
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稳定表达Ras的人成纤维细胞改变自噬活性的细胞效应()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2014年11期
页码:
1578
栏目:
出版日期:
2014-11-15

文章信息/Info

Title:
Cellular response to altered autophagy activity in human fibroblast cells overexpressing
Ha-RasV12
作者:
王玲余乐古春萍李亦蕾
关键词:
自噬Ras早期衰老人成纤维细胞
Keywords:
autophagy Ras premature senescence human fibroblasts
摘要:
目的研究人成纤维细胞稳定过度表达癌基因Ras 对自噬的影响。方法以自噬抑制剂氯喹、自噬关键基因ATG7 的
siRNA、自噬促进剂雷帕霉素处理转染了H-RasV12或空载体的BJ细胞,观察其对细胞增殖、衰老和死亡指标的影响。结果氯
喹处理后,Ras稳定过度表达的BJ细胞衰老现象更加明显且细胞死亡率显著升高,ATG7 siRNA亦可以促进细胞衰老,而雷帕霉
素处理后死亡率同样显著升高,但存活细胞的衰老减轻。在对照细胞,氯喹促进细胞衰老和死亡的细胞效应发生迟缓,ATG7
siRNA和雷帕霉素处理则无明显作用。结论人成纤维细胞稳定过度表达癌基因Ras后,自噬活性受到抑制且抑制程度受到严
格的控制,改变自噬活性可对细胞衰老和存活产生显著影响。
Abstract:
Objective To study the effect of oncogenic Ras overexpression on autophagic activity in human fibroblast cells in
vitro. Methods BJ cells were transfected with H-RasV12 or control vector and treated with chloroquine, small interfering RNA
(siRNA) for ATG7, or rapamycin. The cellular responses were analyzed by monitoring the parameters and biomarkers for cell
growth, senescence and cell death. Results In BJ cells overexpressing H-RasV12, chloroquine treatment resulted in more
prominent cell senescence and a significantly increased cell death rate. Suppression of ATG7 mediated by siRNA also
promoted cell senescence. Rapamycin treatment also caused an increased cell death rate but attenuated senescence in
surviving cells. In control BJ cells, the cellular response to chloroquine included senescence and cell death, which occurred
slowly. Rapamycin treatment and siRNA suppression of ATG7 had no obvious effect on control BJ cells. Conclussion Stable
cellular overexpression of oncogenic Ras causes tightly controlled suppression of the autophagic activity of human fibroblast
cells, and such changes produce significant effect on cell senescence and survival.

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更新日期/Last Update: 1900-01-01