Zhang Jian, Mao Tao, Wang Shuyun, Wang Dongsheng, Niu Zhaojian, Sun Zhenqing, Zhang Jianli
Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
Oncotarget. 2017 May 10;8(42):71563-71573. doi: 10.18632/oncotarget.17751. eCollection 2017 Sep 22.
Colon cancer development is closely related to inflammation. Thus, we conducted the present investigation to study the effects of IL-35 (Interleukin 35), a newly identified anti-inflammatory factor, on colon cancer development. We first evaluated the IL-35 expression in 186 pairs of colon cancer samples and paired adjacent normal tissues by qPCR, ELISA (Enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-35 on patient survival rates, colon cancer progression and their sensitivity to chemotherapy drugs were assessed. IL-35 was barely expressed in the colon cancer tissue but highly expressed in the adjacent normal tissue. The down-regulation of IL-35 was significantly associated with the AJCC (American Joint Committee on Cancer) stage, nodal involvement, invasion depth, distant metastasis, differentiation and it was also shown to be an independent prognostic indicator of both disease-free and overall survivals for colon cancer patients. Overexpression of IL-35 in colon cancer cell suppressed cell migration, invasion, proliferation, colony formation and cancer stem cells through suppressing β-catenin. IL-35 inhibited colon tumor formation in the mice model and sensitize the cancer cell to chemotherapy drugs. Our results showed that IL-35 shows an inhibitory effect in colon cancer development and is a novel prognostic indicator. Therefore, IL-35 might be a potential therapeutic target.
结肠癌的发生与炎症密切相关。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）对结肠癌发生的影响。我们首先通过定量聚合酶链反应（qPCR）、酶联免疫吸附测定（ELISA）和组织芯片，评估了186对结肠癌样本及其配对的相邻正常组织中IL-35的表达情况。然后评估了IL-35对患者生存率、结肠癌进展及其对化疗药物敏感性的作用。IL-35在癌组织中几乎不表达，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（AJCC）分期、淋巴结受累、浸润深度、远处转移、分化显著相关，并且它也是结肠癌患者无病生存期和总生存期的独立预后指标。在结肠癌细胞中过表达IL-35可通过抑制β-连环蛋白来抑制细胞迁移、侵袭、增殖、集落形成和癌症干细胞。IL-35抑制小鼠模型中的结肠肿瘤形成，并使癌细胞对化疗药物敏感。我们的结果表明，IL-35在结肠癌发生中显示出抑制作用，并且是一种新的预后指标。因此，IL-35可能是一个潜在的治疗靶点。
