Li Wenya, Xu Jian, Zhao Jian, Zhang Rui
Department of Internal Medicine, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang, Liaoning, China (mainland).
Department of Colorectal Surgery, Cancer Hospital of China Medical University (Liaoning Cancer Hospital and Institute), Shenyang, Liaoning, China (mainland).
Med Sci Monit. 2017 Feb 12;23:780-789. doi: 10.12659/msm.901880.
BACKGROUND Colon cancer is one of the most common malignant cancers and causes millions of deaths each year. There are still no effective treatments for colon cancer patients who are at advanced stage. Tumor necrosis factor-alpha (TNF-α) might be a good therapy target due to its widely-accepted roles in regulating multiple important biological processes, especially in promoting inflammation. MATERIAL AND METHODS We evaluated the expression of TNF-α in 108 human colon cancer tissue samples and 2 colon cancer cell lines (CT26 and HCT116), and analyzed its prognostic values. Further, we explored the roles and mechanism of anti-TNF-α treatment in combination with chemotherapy in vitro and in vivo. RESULTS We found that TNF-α was highly expressed in colon cancer cell lines. The survival analysis and Cox regression analysis indicated that high TNF-α was an independent adverse prognosticator of colon cancer. In addition, anti-TNF-α treatment enhanced the effects of chemotherapy in the xenograft mouse model through inducing ADCC and CDC effects. CONCLUSIONS We conclude that TNF-α is an independent adverse prognosticator of colon cancer, and anti-TNF-α might benefit colon cancer patients.
结肠癌是最常见的恶性肿瘤之一,每年导致数百万人死亡。对于晚期结肠癌患者,目前仍没有有效的治疗方法。肿瘤坏死因子-α(TNF-α)可能是一个很好的治疗靶点,因为它在调节多个重要生物学过程中发挥着广泛认可的作用,尤其是在促进炎症方面。
我们评估了108例人类结肠癌组织样本和2种结肠癌细胞系(CT26和HCT116)中TNF-α的表达,并分析了其预后价值。此外,我们在体外和体内探索了抗TNF-α治疗联合化疗的作用及机制。
我们发现TNF-α在结肠癌细胞系中高表达。生存分析和Cox回归分析表明,高TNF-α是结肠癌独立的不良预后因素。此外,抗TNF-α治疗通过诱导抗体依赖的细胞介导的细胞毒性(ADCC)和补体依赖的细胞毒性(CDC)效应,增强了异种移植小鼠模型中化疗的效果。
我们得出结论,TNF-α是结肠癌独立的不良预后因素,抗TNF-α可能使结肠癌患者受益。