Sign up for Table of Contents Alerts.
Cell Cycle is published 24 times a year.
Email this page
Print this page
Report
Silencing of LMP1 Induces Cell Cycle Arrest and Enhances Chemosensitivity Through Inhibition of AKT Signaling Pathway in EBV-Positive Nasopharyngeal Carcinoma Cells
Yu-Ping Mei, Jun-Min Zhou, Yi Wang, He Huang, Rong Deng, Gong-Kan Feng, Yi-Xin Zeng and Xiao-Feng Zhu
volume 6 | issue 11
1 June 2007Pages: 1379 - 1385
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). In this study, we investigated that the effect of silencing LMP1 on cell cycle distribution and chemosensitivity in EBV-positive nasopharyngeal carcinoma C666-1 cells. Silencing of LMP1 by specific siRNA induced G1 arrest in C666-1 cells. The protein expression of CDK4 and cyclin D1 decreased and P27 was upregulated following LMP1 knockdown. Phosphorylation of AKT and its downstream targets IКB, FKHR was inhibited by LMP1 siRNA. The chemosensitivity of C666-1 cells to bleomycin and cisplatin was enhanced by siRNA targeting LMP1. The cells treated with LMP1 siRNA showed enhanced cleavage of the effector caspase3 and PARP, and Bax had the tendency to exhibit higher expression. Also, co-transfection of constitutive active AKT plasmid with LMP-1 siRNA plasmid abrogates sensitivity of C666-1 to bleomycin and cisplatin. It is reported for the first time that AKT signaling pathway was directly involved in the effects induced by siRNA targeting LMP1. Our findings confirm LMP1 as a rational therapeutic target in NPC.
Authors
Yu-Ping Mei
Sun Yat-sen University, Guangzhou, China
Jun-Min Zhou
Sun Yat-sen University, Guangzhou, China
Yi Wang
He Huang
Sun Yat-sen University, Guangzhou, China
Rong Deng
State Key Laboratory of Oncology in South China; Cancer Center; Sun Yat-sen University; Guangzhou China
Gong-Kan Feng
Sun Yat-sen University, Guangzhou, China
Yi-Xin Zeng
State Key Laboratory of Oncology in South China; and Sun Yat-sen University Cancer Center
Xiao-Feng Zhu
State Key Laboratory of Oncology in South China; Cancer Center; Sun Yat-sen University; Guangzhou China
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.