PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways

  • Authors:
    • Xiaohui Xu
    • Yushang Cui
    • Lei Cao
    • Ye Zhang
    • Yan Yin
    • Xue Hu
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  • Published online on: March 10, 2017     https://doi.org/10.3892/etm.2017.4218
  • Pages: 1993-1999
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Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilisin family of PCs that encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 in lung cancer cell apoptosis has remained elusive. In the present study, A549 human lung adenocarcinoma cells were transfected with PCSK9 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. The results indicated that PCSK9 siRNA exhibited anti‑tumor activity by inducing apoptosis as determined by a Cell Counting Kit‑8 and Hoechst staining analysis. In addition, PCSK9 siRNA significantly increased apoptosis of A549 cells in part via activation of caspase‑3 and downregulation of the anti‑apoptotic proteins survivin and X‑linked inhibitor of apoptosis protein. Moreover, the results demonstrated that perturbations in the mitochondrial membrane were associated with the deregulation of the Bax/Bcl-2 ratio, which led to the release of cytochrome c after PCSK9 siRNA transfection. In addition, PCSK9 siRNA also induced endoplasmic reticulum stress (ERS) by increasing the levels of 78 kDa glucose‑regulated protein (GRP78), GRP94, phosphorylated protein kinase R‑like ER kinase and phosphorylated eukaryotic initiation factor 2α. Therefore, these results demonstrated that PCSK9 siRNA may exert its anti-tumor activity through inducing mitochondrial dysfunction and ERS-associated cell death in A549 cells.
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May-2017
Volume 13 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Xu X, Cui Y, Cao L, Zhang Y, Yin Y and Hu X: PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways. Exp Ther Med 13: 1993-1999, 2017
APA
Xu, X., Cui, Y., Cao, L., Zhang, Y., Yin, Y., & Hu, X. (2017). PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways. Experimental and Therapeutic Medicine, 13, 1993-1999. https://doi.org/10.3892/etm.2017.4218
MLA
Xu, X., Cui, Y., Cao, L., Zhang, Y., Yin, Y., Hu, X."PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways". Experimental and Therapeutic Medicine 13.5 (2017): 1993-1999.
Chicago
Xu, X., Cui, Y., Cao, L., Zhang, Y., Yin, Y., Hu, X."PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways". Experimental and Therapeutic Medicine 13, no. 5 (2017): 1993-1999. https://doi.org/10.3892/etm.2017.4218