STAT3抑制治疗性结肠炎与结直肠癌相关的结直肠癌
Prema Robinson1, Zal Italia1, Zara Italia1
1Departments of Infectious Diseases, Infection Control & Employee Health, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
在炎症性肠病 (IBD) 的小鼠模型中,使用TTI-101抑制STAT3显著降低了结直肠癌 (CRC) 的发展. 这种STAT3抑制剂在治疗IBD相关的CRC方面表现有前途.
科学领域:
- 在瘤学瘤学.
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 炎症性肠病 (IBD) 患者患结肠直肠癌 (CRC) 的风险明显更高.
- 在IBD患者中,结肠直肠癌通常在晚期被诊断出来,预后较差.
- 针对STAT3信号是一种潜在的治疗策略,用于IBD相关的CRC.
研究的目的:
- 评估小分子STAT3抑制剂TTI-101在大肠炎相关结肠直肠癌小鼠模型中的疗效.
- 确定以TTI-101准STAT3是否可以减少瘤的发展,并调节相关的分子通路.
主要方法:
- 甲 (AOM) - 二硫酸盐 (DSS) 鼠标模型被用于诱导结肠炎相关的CRC.
- 在28天的时间里,小鼠通过口腔 gavage 接受了TTI-101 (50 mg/kg) 或载体治疗.
- 分析了腺瘤数量,激活STAT3 (pY-STAT3) 的水平,以及结肠转录组.
主要成果:
- 与载体对照组相比,TTI-101治疗使腺瘤数量减少了89% (p ≤0.05).
- 活化STAT3水平在失塑性粘膜上升,与腺瘤数量相关.
- 在血和结肠组织中检测到TTI-101,其水平与pY-STAT3.3相反相关.
- TTI-101使结肠转录组正常化,并减少了致癌性STAT3/STAT1上调基因的表达.
结论:
- 在与大肠炎相关的CRC小鼠模型中,TTI-101有效抑制瘤发育.
- STAT3信号传递是IBD相关的CRC瘤发生的关键驱动因素.
- TTI-101显示出作为治疗性治疗剂的潜力,用于患有CRC的IBD患者.
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