Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Department of Biochemistry, Semnan University of Medical Sciences, Semnan, Iran.
J Gastrointest Cancer. 2021 Jun;52(2):454-461. doi: 10.1007/s12029-021-00587-0. Epub 2021 Jan 23.
INTRODUCTION : Colorectal cancer (CRC) is one of the important gastrointestinal tract tumors. Heme is mainly absorbed in the colon and induces nitrosamine formation, genotoxicity, and oxidative stress, and increases the risk of CRC.
Information was collected from articles on Scopus, Google Scholar, and PubMed.
Heme can irritate intestinal epithelial cells and increases the proliferation of colonic mucosa. Heme can be considered as a carcinogenic agent for CRC induction. In typical situations, Heme Oxygenase-1 (HO-1) is expressed at low concentration in the gastrointestinal tract, but its expression is elevated during lesion and inflammation. Based on the multiple reports, the impact of HO-1 on tumor growth is related to the cancer cell type. Increased HO-1 levels were also indicated in different human and animal malignancies, possibly through its contribution to tumor cell growth, metastasis, expression of angiogenic factors, and resistance to chemotherapy. Recent studies noted that HO-1 can act as an immunomodulator that suppresses immune cell maturation, activation, and infiltration. It also inhibits apoptosis through CO production that leads to p53 suppression. The upregulation of HO-1 significantly increases the endurance of colon cancer cell lines. Therefore, it is supposed that HO-1 inhibitors could become a novel antitumor agent. Lactobacillus rhamnosus and its metabolites can activate Nrf2 and improves anti-oxidant levels along with upregulation of its objective genes like HO-1, and downregulation of NF-κB which reduce phosphorylated TNF-α, IL-1β, and PAI-1.
The precise mechanism accountable for the anti-inflammatory features of HO-1 is not completely understood; nevertheless, the CO signaling function associated with the antioxidant property shown by bilirubin possibly will play an act in the improvement of inflammation.
介绍：结直肠癌（CRC）是重要的消化道肿瘤之一。血红素主要在结肠中被吸收，并诱导亚硝胺形成、遗传毒性和氧化应激，增加 CRC 的风险。
从 Scopus、Google Scholar 和 PubMed 上的文章中收集信息。
血红素可刺激肠道上皮细胞，增加结肠黏膜的增殖。血红素可被视为 CRC 诱导的致癌剂。在典型情况下，血红素加氧酶-1（HO-1）在胃肠道中的表达浓度较低，但在病变和炎症时表达升高。根据多项报告，HO-1 对肿瘤生长的影响与癌细胞类型有关。在不同的人和动物恶性肿瘤中也观察到 HO-1 水平升高，可能通过其对肿瘤细胞生长、转移、血管生成因子表达和化疗耐药性的贡献。最近的研究表明，HO-1 可以作为一种免疫调节剂，抑制免疫细胞成熟、激活和浸润。它还通过 CO 产生抑制细胞凋亡，导致 p53 抑制。HO-1 的上调显著增加了结肠癌细胞系的耐受力。因此，HO-1 抑制剂可能成为一种新型抗肿瘤药物。鼠李糖乳杆菌及其代谢物可以激活 Nrf2，并提高抗氧化水平，同时上调其靶基因如 HO-1，并下调 NF-κB，从而降低磷酸化 TNF-α、IL-1β 和 PAI-1。
HO-1 抗炎作用的确切机制尚不完全清楚；然而，胆红素所显示的 CO 信号功能与抗氧化特性可能在改善炎症方面发挥作用。
