Effect of etoposide-induced alteration of the Mdm2-Rb signaling pathway on cellular senescence in A549 lung adenocarcinoma cells.
Effect of etoposide-induced alteration of the Mdm2-Rb signaling pathway on cellular senescence in A549 lung adenocarcinoma cells.
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DOI：
10.3892/ol.2017.6684
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发表时间：
2017-10
期刊：
影响因子：
2.9
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Dai W;Jiang Y;Chen K;Qiu J;Sun J;Zhang W;Zhou X;Huang N;Li Y;Li W
本研究旨在探讨不同浓度的依托泊苷（VP-16）对A549肺腺癌细胞衰老过程中E3泛素-蛋白连接酶Mdm 2（Mdm 2）-视网膜母细胞瘤（Rb）信号通路的影响。将A549细胞随机分为以下四组：对照组（未处理）、组1（1 µmol/l VP-16）、组2（5 µmol/l VP-16）和组3（25 µmol/l VP-16）。各组处理后培养48 h，观察细胞形态学变化。流式细胞仪检测各组细胞周期分布。此外，测定细胞衰老相关β-半乳糖苷酶的活性以及Mdm 2和磷酸化（p-）Rb蛋白的表达。与对照组相比，VP-16处理后衰老细胞的百分比显著更高。VP-16处理组G1期细胞百分率、p-Rb蛋白和Mdm 2蛋白表达与对照组相比也有显著性差异。VP-16可提高A459细胞β-半乳糖苷酶的活性。VP-16还可降低Mdm 2和p-Rb蛋白的表达水平，并抑制G1期细胞周期进程。这些结果表明VP-16通过Mdm 2-Rb信号通路诱导A549细胞衰老。然而，需要进一步的研究来验证VP-16这些作用的机制。
The present study aimed to investigate the effect of various concentrations of etoposide (VP-16) on the E3 ubiquitin-protein ligase Mdm2 (Mdm2)-retinoblastoma (Rb) signaling pathway in the cellular senescence of A549 lung adenocarcinoma cells. A549 cells were randomly divided into the following four groups: Control group (no treatment), group 1 (1 µmol/l VP-16), group 2 (5 µmol/l VP-16) and group 3 (25 µmol/l VP-16). Each group was cultured for 48 h after treatment prior to observation of the alterations to cellular morphology. The cell cycle distribution of each group was also detected by flow cytometry. In addition, the activity of cellular senescence-associated β-galactosidase, and the expression of Mdm2 and phosphorylated (p-) Rb protein, was measured. The percentage of senescent cells was significantly higher following VP-16 treatment compared with the control group. The percentage of G1 phase cells, and p-Rb protein and Mdm2 protein expression were also significantly different following VP-16 treatment compared with the control group. VP-16 increased the activity of β-galactosidase in the A459 cells. VP-16 also decreased the expression level of Mdm2 and p-Rb protein and inhibited cell cycle progression in G1. These results indicate that VP-16 induces the cellular senescence of A549 cells via the Mdm2-Rb signaling pathway. However, further investigations are required to validate the mechanisms underlying these effects of VP-16.
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影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
4.3
作者：
Crane, Edward J;Simon, George
通讯作者：
Simon, George
DOI：
10.1158/1541-7786.mcr-15-0089
发表时间：
2015-08
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Carrillo AM;Hicks M;Khabele D;Eischen CM
通讯作者：
Eischen CM