Chen Xuhui, Lu Kuanchang, Timko Noah J, Weir Dylan M, Zhu Ziwen, Qin Chenglu, Mann Jeffery D, Bai Qian, Xiao Huaping, Nicholl Michael B, Wakefield Mark R, Fang Yujiang
Department of Surgery, Luohu Hospital, Shenzhen, Guangdong 518000, P.R. China.
Department of Microbiology, Immunology and Pathology, Des Moines University College of Osteopathic Medicine, Des Moines, IA 50312, USA.
Oncol Lett. 2018 Jul;16(1):769-774. doi: 10.3892/ol.2018.8728. Epub 2018 May 16.
Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells. The effects of IL-33 on proliferation, cell survival and apoptosis on human HCT-116 colon cancer cells were examined using clonogenic survival assays, proliferation and caspase-3 activity kits, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining and immunocytochemistry. It was determined that the HCT-116 cells demonstrated an notable decrease in optical density value upon incubation with IL-33, along with a decrease in the number of colonies, compared with the controls. It was further determined that the anti-proliferative effect of IL-33 on HCT-116 cells was associated with downregulation of the pro-proliferative molecules cyclin B, cyclin D and cyclin dependent kinase 2. An apoptosis-inducing effect of IL-33 on HCT-116 cells was associated with downregulation of the anti-apoptotic molecules Flice-like inhibitory protein and B-cell lymphoma 2. Taken together, the results indicated that IL-33 inhibits the growth of colon cancer by suppressing cellular proliferation, whilst simultaneously promoting apoptosis.
白细胞介素-33(IL-33)是一种损伤相关分子模式分子,属于白细胞介素-1家族的一种细胞因子,可与多种细胞类型的质膜受体肿瘤抑制因子2结合。IL-33在自身免疫性疾病、宿主对病原体和过敏原的反应中的作用已得到广泛研究,并且在癌症研究中与致癌作用相关。本研究基于先前已证明IL-33对胰腺癌细胞具有抗肿瘤作用的数据,旨在研究IL-33对结肠癌细胞的影响。使用克隆形成存活试验、增殖和半胱天冬酶-3活性试剂盒、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色和免疫细胞化学检测了IL-33对人HCT-116结肠癌细胞增殖、细胞存活和凋亡的影响。结果发现,与对照组相比,HCT-116细胞在与IL-33孵育后光密度值显著降低,集落数量也减少。进一步确定,IL-33对HCT-116细胞的抗增殖作用与增殖分子细胞周期蛋白B、细胞周期蛋白D和细胞周期蛋白依赖性激酶2的下调有关。IL-33对HCT-11细胞的诱导凋亡作用与抗凋亡分子类FLICE抑制蛋白和B细胞淋巴瘤-2的下调有关。综上所述,结果表明IL-33通过抑制细胞增殖同时促进凋亡来抑制结肠癌的生长。