Cellular response to altered autophagy activity in human fibroblast cells overexpressing Ha-RasV12
10.3969/j.issn.1673-4254.2014.11.05
- VernacularTitle:稳定表达Ras的人成纤维细胞改变自噬活性的细胞效应
- Author:
Ling WANG
1
;
Le YU
;
Chunping GU
;
Yilei LI
Author Information
1. 南方医科大学 药学院
- Keywords:
autophagy;
Ras;
premature senescence;
human fibroblasts
- From:
Journal of Southern Medical University
2014;(11):1578-1583
- CountryChina
- Language:Chinese
-
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.
