Abstract
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.
Highlights
Colon cancer is one of the most prevalent malignancies worldwide [1]
Our results showed that IL-35 shows an inhibitory effect in colon cancer development and is a novel prognostic indicator
The data showed that the IL-35 expression decreased at both mRNA and protein levels in colon cancer tissues comparing with its paired adjacent non-cancerous tissues (Figure 1A and 1B), and this was further confirmed by western blot analysis (Figure 1C)
Summary
Colon cancer is one of the most prevalent malignancies worldwide [1]. It is estimated that over half of the patients with colon cancer had developed distant metastasis [2]. Identifying more biomarkers, uncovering the mechanisms underlying colon cancer development and novel therapeutic targets development are necessary. Colon cancer development is a multistage process, which originated from normal mucosa, and adenomatous polyps, carcinoma, and invasive and metastatic carcinoma [3]. Previous studies have demonstrated that multiple mechanisms are responsible for the colon cancer development. Growing evidences indicate that immune mechanisms are crucial in colon cancer progression [4]. Dysregulated inflammatory response and pro-inflammatory cytokines are related to tumor development, including growth, metastasis, apoptosis and angiogenesis [5]. IL-35 consists of two subunits, EBI3 (Epstein-Barr virus induced gene 3) and p35 [6]
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