Effects on apoptosis and cell cycle arrest contribute to the antitumor responses of interleukin-27 mediated by retrovirus in human pancreatic carcinoma cells

Abstract

Abstract. Interleukin (IL)-27, composed of p28 and EpsteinBarr 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 (AsPC1) by retroviral vector would produce IL-27-mediated antitumor effects and the related mechanisms. The data demonstrated that AsPC1 cells expressed both IL-27 receptor subunits, and tumor growth of AsPC1/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-γ, tumor necrosis factor-α and IL-1β in tumor specimens increased, while the secretion of IFN-γ and TNF-α from spleen cells of mice bearing IL-27-transfected tumors increased. Moreover, cell cycle arrest was induced in AsPC1/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.

Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin

“…In general, IL-27 modulates immunologic function that expresses by either proinflammatory or anti-inflammatory effects. In cancer cells, IL-27 can activate apoptosis via several pathways as presented in some reports [35,36]. A549 cell is derived from adenocarcinoma origin.…”

Emerging roles for the IL-6 family of cytokines in pancreatic cancer

“…Both pro-and anti-tumorigenic roles have been suggested for IL-27, depending on the cancer type examined [ 227 , 228 ]. In PDAC, elevated levels of IL-27 correlate with poor overall survival ( Figure 3 J); however, it has been shown that IL-27 overexpression in PDAC cell line xenograft models exhibited reduced tumour growth, due to increased cell cycle arrest and apoptosis, and increased overall survival [ 229 , 230 ]. It was also shown by in vitro co-culture that IL-27 inhibited the polarisation of TAMs towards an M2 phenotype, thereby reducing cancer cell proliferation, migration, and invasion, inducing cancer cell apoptosis, and improving therapeutic response to gemcitabine [ 231 ].…”

The mechanism of and the association between interleukin‑27 and chemotherapeutic drug sensitivity in lung cancer

“…It has previously been reported that IL-27 directly inhibits cell proliferation and angiogenesis in prostate cancer ( 27 ). Furthermore, transfection of human pancreatic carcinoma cells with IL-27 has previously been reported to inhibit proliferation, induce cell cycle arrest and promote apoptosis ( 28 ). Increasing the expression levels of IL-27, combined with treatment with rapamycin and cisplatin, has been demonstrated to inhibit the proliferation and metastasis of endometrial cancer ( 29 ).…”