Salim Elsayed I, Harras Samar F, Abdalla Aisha G, Mona Mohmmed H
Zoology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
Acta Parasitol. 2018 Mar 26;63(1):198-209. doi: 10.1515/ap-2018-0023.
Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S. muris infection combined with DMH has significantly increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1 after infection has significantly reduced the ACF numbers particularly larger ones. This inhibition was concomitant with significant inhibition in the immunohistochemical levels of the ki67, Caspase-3 and IgM levels in colorectal epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers levels of superoxide dismutase and catalase as well as the non-enzymatic antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis has significantly modulated the oxidative stress markers in the colorectum, while treatment with Bryostatin-1 has exerted significant curative potential. A mechanism could be explained that Bryostatin-1 treatment has reduced oxidative stress markers activities along with affecting host to parasite immunity possibly leading to changes in the COX-2 and APC expression, retarding cellular proliferation and subsequently reducing the colorectal carcinogenesis events.
越来越多的证据表明，某些感染因子可能会干扰肿瘤形成的自然进程。本研究检测了成年鼠管状线虫慢性感染与1,2 - 二甲基肼（DMH）诱导的大鼠结直肠癌发生之间的关联。此外，还研究了海洋苔藓虫Bugulane ritina的有效提取物苔藓抑素 - 1对这种联合作用可能的治疗效果。DMH给药可诱导异常隐窝灶（ACF），这是结直肠癌发生的替代生物标志物，而鼠管状线虫感染与DMH联合使用则显著增加了ACF的总数。尽管如此，感染后用苔藓抑素 - 1治疗可显著减少ACF数量，尤其是较大的ACF。这种抑制作用伴随着结直肠上皮中ki67、半胱天冬酶 - 3和IgM水平以及血清IgM和IgG水平免疫组化水平的显著抑制。此外，鼠管状线虫 + DMH感染后用苔藓抑素 - 1治疗可调节超氧化物歧化酶和过氧化氢酶的酶促抗氧化标志物水平以及还原型谷胱甘肽、脂质过氧化、一氧化氮和总抗氧化能力的非酶促抗氧化标志物水平。此外，用苔藓抑素 - 1治疗可下调结直肠黏膜中COX - 2和APC基因的mRNA表达水平。总之，结直肠癌发生过程中鼠管状线虫感染显著调节了结肠中的氧化应激标志物，而苔藓抑素 - 1治疗具有显著的治疗潜力。可以解释的一种机制是，苔藓抑素 - 1治疗降低了氧化应激标志物的活性，同时影响宿主对寄生虫的免疫力，可能导致COX - 2和APC表达的变化，延缓细胞增殖，进而减少结直肠癌发生事件。
