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Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway
Author(s) -
Ting Xu,
Sihai Wu,
Yuan Yuan,
Guoxin Yan,
Dajiang Xiao
Publication year - 2014
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2014.2422
Subject(s) - nasopharyngeal carcinoma , gene knockdown , epidermal growth factor receptor , cancer research , epidermal growth factor , cell cycle , cell growth , oncogene , phosphodiesterase , pi3k/akt/mtor pathway , protein kinase b , signal transduction , chemistry , biology , cell , cancer , microbiology and biotechnology , apoptosis , medicine , receptor , biochemistry , radiation therapy , enzyme
Phosphodiesterase 4D (PDE4D) is a subtype of metallohydrolases, and it has been reported that PDE4D functions as a proliferation promoting factor in certain types of cancer, including head and neck cancer. The present study first investigated the function of PDE4D in nasopharyngeal carcinoma (NPC). Western blot analysis was applied to detect PDE4D expression in NPC samples and cells. A lentiviral infection technique was used to stabilize the knockdown of PDE4D, which was subsequently examined in vitro and in vivo . The results showed that PDE4D was overexpressed in the NPC tissues and cells. Knockdown of PDE4D inhibited the growth of CNE2 and 5-8F, inducing cell cycle arrest in the G 0 /G 1 phase in CNE2. These effects could be reversed by epidermal growth factor (EGF) stimulation. Furthermore, knockdown of PDE4D significantly inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and AKT. The results were further validated in an NPC xenograft in nude mice. In conclusion, this study demonstrated that PDE4D may function as a proliferation promoting factor in NPC, by affecting the EGFR/PI3K/AKT signaling pathway. Therefore, the targeting of PDE4D may be a rational strategy in the treatment of NPC.

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