Xu Ting, Wu Sihai, Yuan Yuan, Yan Guoxin, Xiao Dajiang
Department of Otolaryngology, The Second People's Hospital of Wuxi, Wuxi, Jiangsu 214002, P.R. China.
Department of Stomatology, The Second People's Hospital of Wuxi, Wuxi, Jiangsu 214002, P.R. China.
Oncol Lett. 2014 Nov;8(5):2110-2116. doi: 10.3892/ol.2014.2422. Epub 2014 Aug 8.
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 and . 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/G 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.
磷酸二酯酶4D(PDE4D)是金属水解酶的一种亚型,据报道,PDE4D在包括头颈癌在内的某些类型癌症中作为增殖促进因子发挥作用。本研究首次探讨了PDE4D在鼻咽癌(NPC)中的功能。采用蛋白质免疫印迹分析检测NPC样本和细胞中PDE4D的表达。利用慢病毒感染技术稳定敲低PDE4D,随后进行检测。结果显示,PDE4D在NPC组织和细胞中过表达。敲低PDE4D可抑制CNE2和5-8F的生长,导致CNE2细胞周期阻滞在G/G期。这些作用可通过表皮生长因子(EGF)刺激逆转。此外,敲低PDE4D显著抑制表皮生长因子受体(EGFR)和AKT的磷酸化。结果在裸鼠NPC异种移植模型中得到进一步验证。总之,本研究表明PDE4D可能通过影响EGFR/PI3K/AKT信号通路在NPC中作为增殖促进因子发挥作用。因此,靶向PDE4D可能是治疗NPC的合理策略。