Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
J Interferon Cytokine Res. 2019 Aug;39(8):483-494. doi: 10.1089/jir.2018.0166. Epub 2019 Apr 22.
Interleukin (IL)-27 is a promising anti-cancer cytokine with therapeutic potential. Exhibiting overlapping properties with type I and II interferons (IFNs), IL-27 impacts cancer cell viability and immune cell activity. Known to modulate toll-like receptor (TLR) expression, we investigated whether IL-27 affected TLR-mediated death in cancer cells. Using DU145 and PC3 cell lines as models of prostate cancer, we investigated whether IL-27 and IFN-γ affect TLR3-mediated cell death. Our results demonstrate that when IL-27 or IFN-γ is added with polyinosinic-polycytidylic acid [poly(I:C)], type I IFN (IFN-I) expression increases concurrently with cell death. IL-27 and IFN-γ enhanced TLR3 expression, suggesting a mechanism for sensitization to cell death. Further, PC3 cells were more sensitive to IL-27/poly(I:C)-induced cell death compared with DU145 cells. This correlated with higher production of IFN-β and inducible protein-10 versus IL-6 in response to treatment of PC3 cells compared with DU145. Taken together, this study demonstrates a potential role for IL-27 in the treatment of prostate cancer.
白细胞介素 (IL)-27 是一种有前景的抗癌细胞因子，具有治疗潜力。它与 I 型和 II 型干扰素 (IFN) 具有重叠的特性，影响癌细胞的活力和免疫细胞的活性。已知 IL-27 可以调节 Toll 样受体 (TLR) 的表达，我们研究了它是否影响 TLR 介导的癌细胞死亡。我们使用 DU145 和 PC3 细胞系作为前列腺癌模型，研究了 IL-27 和 IFN-γ 是否影响 TLR3 介导的细胞死亡。结果表明，当 IL-27 或 IFN-γ 与多聚肌苷酸-多聚胞苷酸 [poly(I:C)] 一起添加时，I 型 IFN (IFN-I) 的表达与细胞死亡同时增加。IL-27 和 IFN-γ 增强了 TLR3 的表达，提示了对细胞死亡敏感的机制。此外，与 DU145 细胞相比，PC3 细胞对 IL-27/poly(I:C)诱导的细胞死亡更敏感。这与 PC3 细胞比 DU145 细胞对治疗产生更高水平的 IFN-β 和诱导蛋白-10 而不是 IL-6 有关。综上所述，这项研究表明 IL-27 在治疗前列腺癌方面具有潜在作用。
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