Sun Mingfei, Zheng Xianjie, Meng Qingjiang, Dong Yanjun, Zhang Guoyu, Rao Dexin, An Xiaokang, Yang Zhongxin, Pan Lihong, Zhang Shuanglin
Cell Physiol Biochem. 2018;51(4):1839-1851. doi: 10.1159/000495706. Epub 2018 Nov 30.
BACKGROUND/AIMS: Lung cancer continues to be the leading cause of cancer related deaths worldwide due to its high incidence, malignant behavior and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers.
We first evaluated the IL-35 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by realtime PCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs were assessed.
IL-35 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The down-regulation of IL-35 was significantly correlated with the results of American Joint Committee on Cancer stage, differentiation and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-35 in NSCLC cells suppressed cell migration, invasion, proliferation, colony formation through suppressing β-catenin. IL-35 inhibited NSCLC formation in the mice model and sensitize the cancer cells to chemotherapy drugs.
Our results showed that IL-35 plays an inhibitory role in NSCLC development and function as a novel prognostic indicator and a potential therapeutic target.
背景/目的：肺癌因其高发病率、恶性行为以及治疗策略缺乏重大进展，仍然是全球癌症相关死亡的主要原因。肺癌的发生和发展与炎症密切相关。因此，我们开展了本研究，以探讨新发现的抗炎因子白细胞介素35（IL-35）对非小细胞肺癌（NSCLC）的影响，非小细胞肺癌约占所有肺癌的85%。
我们首先通过实时PCR、酶联免疫吸附测定（ELISA）和组织芯片评估了384对NSCLC样本及其相邻正常黏膜中的IL-35表达。然后评估了IL-35对患者生存率、癌症进展及其对化疗药物敏感性的作用。
IL-35在NSCLC组织中几乎不表达，但在相邻正常组织中高表达。IL-35的下调与美国癌症联合委员会分期、分化结果显著相关，并且还被证明是NSCLC患者无病生存期和总生存期的独立预后指标。NSCLC细胞中IL-35的过表达通过抑制β-连环蛋白抑制细胞迁移、侵袭、增殖和集落形成。IL-35在小鼠模型中抑制NSCLC形成，并使癌细胞对化疗药物敏感。
我们的结果表明，IL-35在NSCLC发展中起抑制作用，作为一种新的预后指标和潜在的治疗靶点。
