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Programmed Cell Death 4 (PDCD4) Enhances the Sensitivity of Gastric Cancer Cells to TRAIL-Induced Apoptosis by Inhibiting the PI3K/Akt Signaling Pathway

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Abstract

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is thought to be a promising anti-neoplastic agent because of its ability to selectively induce apoptosis in cancer cells. However, some cancer cells are resistant to TRAIL. The mechanisms underlying this resistance are unclear. The aim of this study was to explore the role of programmed cell death 4 (PDCD4) in regulating TRAIL sensitivity in gastric cancer cells.

Methods: PDCD4 complementary DNA and PDCD4-specific short-hairpin RNA (shRNA) fragments were transfected into TRAIL-sensitive and -resistant gastric cancer cells. Expression of PDCD4 and Akt was detected via western blot. Cell survival and apoptosis were measured using 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM) assays.

Results: We found that upregulation of PDCD4 enhanced TRAIL sensitivity in gastric cancer cells. Downregulation of PDCD4 decreased TRAIL sensitivity. Inhibition of Akt by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 induced PDCD4 activity and enhanced TRAIL sensitivity in TRAIL-resistant gastric cancer cells.

Conclusion: We demonstrated that PDCD4 regulates TRAIL sensitivity in gastric cancer cells by inhibiting the PI3K/Akt signaling pathway.

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Acknowledgments

Wei-Qiang Wang and Hao Zhang contributed equally to this work. The work was financially supported by the Scientific Research Foundation of the Chinese People’s Liberation Army, during the 10th Five-Year Plan Period, No. 01MA172.

The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, China

    Wei-Qiang Wang, Hao Zhang, Hong-Bin Wang, Yong-Gang Sun, Zhi-Hong Peng, Gang Zhou, Shi-Ming Yang, Rong-Quan Wang &  Dian-Chun Fang

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  1. Wei-Qiang Wang
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Correspondence to Dian-Chun Fang.

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Wang, WQ., Zhang, H., Wang, HB. et al. Programmed Cell Death 4 (PDCD4) Enhances the Sensitivity of Gastric Cancer Cells to TRAIL-Induced Apoptosis by Inhibiting the PI3K/Akt Signaling Pathway. Mol Diag Ther 14, 155–161 (2010). https://doi.org/10.1007/BF03256368

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