Effects of Three IL-15 Variants on NCI-H446 Cell Proliferation and Expression of Cell Cycle Regulatory Molecules

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 4

PMID 29296227

Citations 1

Authors

Jun-Ying Ding

Zhi-Hua Wang

Zheng-Zheng Zhang

Xu-Ran Cui

Yan-Ying Hong

Qing-Quan Liu

Affiliations

Soon will be listed here.

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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PMID: 35540501 PMC: 9080254. DOI: 10.1039/c8ra02580k.

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