Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, P.O Box 566, Irbid, 21163, Jordan.
Department of Biological Sciences, Faculty of Science, Yarmouk University, Irbid, Jordan.
BMC Cancer. 2023 Aug 2;23(1):722. doi: 10.1186/s12885-023-11195-5.
It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered.
To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer.
BALB/c mice with azoxymethane/dextran sodium sulfate (AOM/DSS)-induced colitis-associated colorectal cancer (CAC), we intraperitoneally treated with commercial preparation of human plasma AAT (4 mg per mouse). Effects of this therapy were evaluated histologically, and by immunohistochemical and gene expression assays.
When compared with non-treated controls, AOM/DSS mice receiving AAT therapy exhibited significantly longer colons, and less anal bleeding. Concurrently, AAT-treated mice had significantly fewer polyps, and lower numbers of large colon tumors. Immunohistochemical examinations of colon tissues showed significantly lower neutrophil counts, more granzyme B-positive but fewer MMP9 (gelatinase B)-positive cancer cells and lower numbers of apoptotic cells in mice receiving AAT therapy. The expression levels of IL4 were significantly higher while TNFA was slightly reduced in tumor tissues of AOM/DSS mice treated with AAT than in AOM/DSS mice.
Human AAT is an acute phase protein with a broad-protease inhibitory and immunomodulatory activities used as a therapeutic for emphysema patients with inherited AAT deficiency. Our results are consistent with previous findings and support an idea that AAT alone and/or in combination with available anti-cancer therapies may represent a new personalized approach for patients with colitis-induced colon cancer.
慢性炎症性肠病显著增加了结直肠癌发展的风险，这一点已被广泛接受。在结肠癌患者的不同治疗类型中，新型蛋白质治疗策略受到关注。
探讨人血浆α-1 抗胰蛋白酶（AAT）蛋白在化学诱导的结直肠癌小鼠模型中的作用。
使用氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）诱导的结肠炎相关结直肠癌（CAC）小鼠模型，我们通过腹腔内给予商业制备的人血浆 AAT（每只小鼠 4 毫克）进行治疗。通过组织学、免疫组织化学和基因表达分析评估这种治疗的效果。
与未治疗的对照组相比，接受 AAT 治疗的 AOM/DSS 小鼠的结肠明显更长，肛门出血更少。同时，AAT 治疗的小鼠息肉更少，大结肠肿瘤数量也更少。对结肠组织的免疫组织化学检查显示，接受 AAT 治疗的小鼠中性粒细胞计数明显降低，颗粒酶 B 阳性但 MMP9（明胶酶 B）阳性癌细胞和凋亡细胞数量减少。与 AOM/DSS 小鼠相比，接受 AAT 治疗的 AOM/DSS 小鼠肿瘤组织中 IL4 的表达水平明显升高，而 TNFA 略有降低。
人 AAT 是一种具有广泛蛋白酶抑制和免疫调节活性的急性期蛋白，用于治疗遗传性 AAT 缺乏症的肺气肿患者。我们的结果与之前的发现一致，支持 AAT 单独或与现有的抗癌疗法联合使用可能代表一种针对结肠炎诱导的结肠癌患者的新的个性化治疗方法的观点。
