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IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells

Long, Jun, Zhang, Xulong, Wen, Mingjie, Kong, Qingli, Lv, Zhe, An, Yunqing and Wei, Xiao-Qing 2013. IL-35 over-expression increases apoptosis sensitivity and suppresses cell growth in human cancer cells. Biochemical and Biophysical Research Communications 430 (1) , pp. 364-369. 10.1016/j.bbrc.2012.11.004

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Interleukin (IL)-35 is a novel heterodimeric cytokine in the IL-12 family and is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. IL-35 is expressed in T regulatory (Treg) cells and contributes to the immune suppression function of these cells. In contrast, we found that both IL-35 subunits were expressed concurrently in most human cancer cell lines compared to normal cell lines. In addition, we found that TNF-α and IFN-γ stimulation led to increased IL-35 expression in human cancer cells. Furthermore, over-expression of IL-35 in human cancer cells suppressed cell growth in vitro, induced cell cycle arrest at the G1 phase, and mediated robust apoptosis induced by serum starvation, TNF-α, and IFN-γ stimulation through the up-regulation of Fas and concurrent down-regulation of cyclinD1, survivin, and Bcl-2 expression. In conclusion, our results reveal a novel functional role for IL-35 in suppressing cancer activity, inhibiting cancer cell growth, and increasing the apoptosis sensitivity of human cancer cells through the regulation of genes related to the cell cycle and apoptosis. Thus, this research provides new insights into IL-35 function and presents a possible target for the development of novel cancer therapies.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: IL-35; Human cancer; Growth; Cell cycle; Apoptosis
Publisher: Elsevier
ISSN: 0006-291X
Last Modified: 04 Jun 2017 04:34

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