Effect of etoposide-induced alteration of the Mdm2-Rb signaling pathway on cellular senescence in A549 lung adenocarcinoma cells

Dai,Wenjing; Jiang,Yi; Chen,Kairong; Qiu,Jing; Sun,Jian; Zhang,Wei; Zhou,Xiafei; Huang,Na; Li,Yunhui; Li,Wancheng

doi:10.3892/ol.2017.6684

Effect of etoposide-induced alteration of the Mdm2-Rb signaling pathway on cellular senescence in A549 lung adenocarcinoma cells

Authors:
- Wenjing Dai
- Yi Jiang
- Kairong Chen
- Jing Qiu
- Jian Sun
- Wei Zhang
- Xiafei Zhou
- Na Huang
- Yunhui Li
- Wancheng Li
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Affiliations: Department of Respiration, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Respiration, People's Hospital of Meishan, Meishan, Sichuan 620000, P.R. China
Published online on: July 27, 2017 https://doi.org/10.3892/ol.2017.6684
Pages: 3935-3940
Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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