Effects on apoptosis and cell cycle arrest contribute to the antitumor responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma cells
Effects on apoptosis and cell cycle arrest contribute to the antitumor responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma cells
复制标题
对细胞凋亡和细胞周期停滞的影响有助于人胰腺癌细胞中逆转录病毒介导的白介素 27 的抗肿瘤反应
DOI：
10.3892/or.2012.1663
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发表时间：
2012-05-01
期刊：
影响因子：
4.2
通讯作者：
Shan, Baoen
中科院分区：
文献类型：
--
作者：
Liu, Lihua;Meng, Jun;Shan, Baoen
Interleukin (IL)-27, composed of p28 and Epstein-Barr virus-induced gene 3 (EBI3) subunits, has diverse functions in regulating immune systems. Human melanoma cells have been shown to express both IL-27 receptor subunits, and growth inhibition by IL-27 was detected. We investigated whether forced expression of the p28-linked EBI3 gene in human pancreatic carcinoma cells (AsPCl) by retroviral vector would produce IL-27-mediated antitumor effects and the related mechanisms. The data demonstrated that AsPCl cells expressed both IL-27 receptor subunits, and tumor growth of AsPCl/IL-27 in mice was retarded compared with vector DNA-transduced tumors and survival of the mice was prolonged. Expression of cytokines such as interferon-gamma, tumor necrosis factor-alpha and IL-1 beta in tumor specimens increased, while the secretion of IFN-gamma and TNF-alpha from spleen cells of mice bearing 11,27-transfected tumors increased. Moreover, cell cycle arrest was induced in AsPCl/IL-27 inoculated mice with upregulated p21 expression and downregulated survivin expression. The appearance of apoptotic cells increased in tumor specimens of mice bearing IL-27-transfected tumors compared with the mice bearing DNA-transfected tumors by confirming the expression of apoptosis-related proteins and activated apoptotic pathways through detection of cleaved PARP. These results suggest that transfection of the IL-27 gene into human pancreatic carcinoma cells could produce antitumor effects in vivo and induction of cell cycle arrest and apoptosis could be the mechanism of IL-27 action in tumor regression.
