Liao Jie, Seril Darren N, Yang Allison L, Lu Gary G, Yang Guang-Yu
Department of Pathology, Northwestern University, Feinberg School of Medicine 303 East Chicago Avenue, Chicago, IL 60611, USA.
Carcinogenesis. 2007 Feb;28(2):446-54. doi: 10.1093/carcin/bgl154. Epub 2006 Sep 14.
Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle=7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26+/-1.05 and tumor volume was 21.4+/-5.2 mm3. Adding 1% inositol, tumor incidence was statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor multiplicity (0.5+/-0.7) and tumor volume (4.2+/-1.9 mm3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with tumors out of 24 total), tumor multiplicity (0.8+/-0.9) and tumor volume (12.3+/-4.1 mm3); however, the results were not statistically significant (P>0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.
慢性炎症是公认的癌症风险因素，长期患有溃疡性结肠炎（UC）的患者患结直肠癌的风险增加。为了预防UC相关的致癌作用，我们在新型小鼠模型中测试了肌醇化合物（包括肌醇和肌醇六磷酸）对UC相关致癌作用的影响。雌性C57BL/6小鼠接受长期、周期性的葡聚糖硫酸钠（DSS）处理，并喂食富含两倍铁的饮食。肌醇化合物通过饮用水给药。在DSS加两倍铁阳性对照组中，经过15个周期的DSS处理（1个DSS周期=7天DSS处理期，随后是10天恢复期）后，结直肠癌发病率为70.6%（24/34只小鼠）。肿瘤多发性为1.26±1.05，肿瘤体积为21.4±5.2立方毫米。添加1%肌醇后，肿瘤发病率在统计学上显著降低（42%，21只患肿瘤小鼠中的9只），肿瘤多发性（0.5±0.7）和肿瘤体积（4.2±1.9立方毫米）也显著降低。给予肌醇六磷酸可显著降低肿瘤发病率（50%，24只小鼠中有12只患肿瘤）、肿瘤多发性（0.8±0.9）和肿瘤体积（12.3±4.1立方毫米）；然而，结果无统计学意义（P>0.05）。进一步的机制研究表明，肌醇化合物对UC相关致癌作用的抑制可能与其对UC相关致癌过程中巨噬细胞介导的炎症、硝基氧化应激和细胞增殖的调节功能有关。这项研究表明，肌醇化合物可能有潜力作为慢性炎症致癌的预防剂。
