Open Access

ARTICLE

Reduced PDCD4 Expression Promotes Cell Growth Through PI3K/Akt Signaling in Non-Small Cell Lung Cancer

Yan Zhen^*1, Dongming Li^*†1, Wen Li^*, Weimin Yao^*†1, Aibing Wu^‡, Jing Huang^‡, Hongli Gu^*†, Yujie Huang^*†, Yajun Wang^*, Jun Wu^*†, Min Chen^*†, Dong Wu^*†, Quanchao Lyu^*, Weiyi Fang^§, Bin Wu^*†

* Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
† Department of Respiratory Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
‡ Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, PR China
§ Cancer Research Institute, Southern Medical University, Guangzhou, PR China

Oncology Research 2015, 23(1-2), 61-68. https://doi.org/10.3727/096504015X14478843952861

Abstract

It is largely recognized that PDCD4 is frequently lost in tumors of various origins, including lung cancer, and its loss contributes to tumor progression. However, its role and molecular mechanism remain largely unexplored in non-small cell lung cancer (NSCLC). In this study, downregulated PDCD4 mRNA expression was found in NSCLC tissues compared to their corresponding paracarcinoma tissues and distal paracarcinoma tissues. Induced expression of PDCD4 inhibited cell growth and proliferation and cell cycle transition in vitro. Conversely, knocking down PDCD4 expression promoted cell growth and proliferation. Mechanistically, PDCD4 inactivated PI3K/Akt signaling and its downstream cell cycle factors CCND1 and CDK4 to regulate cell growth in NSCLC. Additionally, PI3K-specific inhibitor Ly294002 suppressed the expression of pPI3K (Tyr458), pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Furthermore, Aktspecific inhibitor MK2206 inhibited the expression of pAkt (Ser473), CCND1, and CDK4 in PC9-shPDCD4 and A549-shPDCD4 cells. Taken together, our study provides evidence that PDCD4 inhibits cell growth through PI3K/Akt signaling in NSCLC and may be a potential therapeutic target for NSCLC.

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