Oncotarget

Research Papers:

Effects of three IL-15 variants on NCI-H446 cell proliferation and expression of cell cycle regulatory molecules

Jun-Ying Ding, Zhi-Hua Wang, Zheng-Zheng Zhang, Xu-Ran Cui, Yan-Ying Hong and Qing-Quan Liu _

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Oncotarget. 2017; 8:108108-108117. https://doi.org/10.18632/oncotarget.22550

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Abstract

Jun-Ying Ding1,*, Zhi-Hua Wang2,*, Zheng-Zheng Zhang3, Xu-Ran Cui1, Yan-Ying Hong1 and Qing-Quan Liu1

1Beijing Key Laboratory of Basic Study on Traditional Chinese Medicine (TCM) Infectious Diseases, Beijing Hospital of TCM, Capital Medical University, Beijing Institute of TCM, Beijing, China

2Hebei Key Laboratory of Metabolic Disease, Hebei General Hospital, Shijiazhuang, China

3Department of Immunology and Key Laboratory of Immune Mechanism and Intervention on Serious Disease, Hebei Medical University, Shijiazhuang, China

*These authors have contributed equally to this work

Correspondence to:

Qing-Quan Liu, email: profliu1@126.com

Keywords: interleukin 15; NCI-H446 cells; cell proliferation; cell cycle; cell cycle regulatory molecule

Received: July 13, 2016    Accepted: July 06, 2017    Published: November 20, 2017

ABSTRACT

Interleukin 15 (IL-15) is a cytokine exhibiting antitumor characteristic similar to that of IL-2. However, in human tissues and cells, IL-15 expression and secretion is very limited, suggesting IL-15 functions mainly intracellularly. In the present study, we assessed the effects of transfecting NCI-H446 small cell lung cancer cells with genes encoding three IL-15 variants: prototypical IL-15, mature IL-15 peptide, and modified IL-15 in which the IL-2 signal peptide is substituted for the native signal peptide. NCI-H446 cells transfected with empty plasmid served as the control group. We found that IL-15 transfection effectively inhibited NCI-H446 cell proliferation and arrested cell cycle progression, with the modified IL-15 carrying the IL-2 signal peptide exerting the greatest effect. Consistent with those findings, expression each of the three IL-15 variants reduced growth of NCI-H446 xenograph tumors, and the modified IL-15 again showed the greatest effect. In addition, IL-15 expression led to down-regulation of the positive cell cycle regulators cyclin E and CDK2 and up-regulation of the negative cycle regulators p21 and Rb. These findings suggest IL-15 acts as a tumor suppressor that inhibits tumor cell proliferation by inducing cell cycle arrest.


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