Background/Aims: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. Methods: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. Results: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. Conclusion: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

中文翻译：

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白细胞介素33通过其受体ST2和JNK信号通路预测不良预后并促进肾细胞癌细胞的生长

背景/目的：肾细胞癌（RCC）目前是男性中第九大最常见的癌症。白介素（IL）-33的表达先前已与多种癌症相关。然而，人们对它在RCC中的生物学作用知之甚少。在这项研究中，我们试图阐明IL-33在RCC中的作用。方法：采用ELISA法检测血清IL-33水平。通过免疫细胞化学检查临床RCC样品中的IL-33表达。通过CCK8和流式细胞仪测定RCC的增殖和凋亡率。Mcl1和Bcl-2表达的定量实时荧光定量PCR和Western印迹法。通过蛋白质印迹和流式细胞术测量JNK表达。通过动物模型检查了IL-33在RCC肿瘤发生中的体内作用。结果：我们发现，RCC中IL-33的表达增加与肿瘤淋巴结转移（TNM）阶段有关，并且与预后成反比。IL-33在体内增强RCC细胞的生长并刺激RCC细胞增殖，并在体外阻止化学疗法诱导的肿瘤细胞凋亡。此外，我们证明了IL-33通过其受体ST2和肿瘤细胞中的JNK信号激活来促进RCC细胞增殖和化疗耐药性。结论：我们的发现表明靶向IL-33 / ST2和JNK信号传导可能在RCC的治疗中具有潜在价值。我们证明了IL-33通过其受体ST2和肿瘤细胞中的JNK信号激活来促进RCC细胞增殖和化疗耐药性。结论：我们的发现表明靶向IL-33 / ST2和JNK信号传导可能在RCC的治疗中具有潜在价值。我们证明了IL-33通过其受体ST2和肿瘤细胞中的JNK信号激活来促进RCC细胞增殖和化疗耐药性。结论：我们的发现表明靶向IL-33 / ST2和JNK信号传导可能在RCC的治疗中具有潜在价值。