Genetics and Cancer Research. Research Lab. of Molecular Carcinogenesis, Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
Zoology Department, Faculty of Science, Tanta University, Tanta 31527- Egypt.
Asian Pac J Cancer Prev. 2020 Sep 1;21(9):2739-2750. doi: 10.31557/APJCP.2020.21.9.2739.
In search for a unique natural combination of highly active biological components for treatment against colon cancer, we used aqueous extract of Ascidia, Styela plicata (ASCex), a marine invertebrate depending on its richness of high levels of biologically active components as indicated in our previous studies, against rat colon cancer, exploring its underlying mechanisms.
Rats chemically initiated for colon cancer were either non-treated or post-treated with highly saturated ASCex for 32 weeks after initiation, other groups of rats were administered ASCex without cancer initiation or served as normal controls.
Rats treated with ASCex alone did not show any signs of non-favored health conditions. Treatment with ASCex after cancer initiation has significantly reduced the average incidences, multiplicities and volumes of colon tumors (adenomas and adenocarcinomas) as compared with the non-treated cancer group. ASCex has also significantly reduced the total numbers of aberrant crypt foci (ACF), surrogate biomarkers for colon cancer as compared with the non-treated cancer group. Moreover, anti-proliferative celluar nucular antigen (PCNA) immunohistochemical staining revealed that ASCex exerted significant antiproliferative characteristics in the carcinogen-treated colonic mucosa as compared with its corresponding control. Also, treatment with ASCex has markedly down-regulated the mRNA expression levels of Nuclear Factor-kappa B (NF-κB), a nuclear transcriptional activator as well as the mRNA expression of the cytoplasmic SOD1 gene which encodes Cu/Zn SOD, the first line defense against superoxide radicals.
Collectively, ASCex could act as a potent chemotherapeutic drug against colon cancer, likely through the influence of its rich active metabolites which interfere with various biological pathways including inhibition of protein synthesis during cellular growth and marked induction of antioxidative capacity in the colonic mucosa. This role has been extensively discussed herein.
为了寻找一种具有高度生物活性成分的独特天然组合，用于治疗结肠癌，我们使用了海洋无脊椎动物 Styela plicata（ASCex）的水提物，这是一种基于我们之前的研究表明其富含高水平生物活性成分的海洋无脊椎动物，用于治疗大鼠结肠癌，并探索其潜在机制。
通过化学方法引发大鼠结肠癌后，一组大鼠未进行治疗，另一组大鼠在引发后 32 周用高度饱和的 ASCex 进行后处理，还有一组大鼠未引发癌症但给予 ASCex 作为正常对照。
单独给予 ASCex 的大鼠没有出现任何不利健康状况的迹象。与未治疗的癌症组相比，在癌症引发后给予 ASCex 治疗显著降低了结肠肿瘤（腺瘤和腺癌）的平均发生率、多发性和体积。与未治疗的癌症组相比，ASCex 还显著降低了总异常隐窝病灶（ACF）的数量，ACF 是结肠癌的替代生物标志物。此外，抗增殖细胞核抗原（PCNA）免疫组织化学染色显示，与相应的对照组相比，ASCex 在致癌剂处理的结肠黏膜中表现出显著的抗增殖特性。此外，用 ASCex 治疗明显下调了核转录因子-κB（NF-κB）的 mRNA 表达水平，NF-κB 是一种核转录激活因子，以及编码 Cu/Zn SOD 的细胞质 SOD1 基因的 mRNA 表达，Cu/Zn SOD 是对抗超氧自由基的第一道防线。
总之，ASCex 可能作为一种有效的结肠癌化疗药物，其作用机制可能是通过其丰富的活性代谢物干扰多种生物学途径，包括抑制细胞生长过程中的蛋白质合成以及显著诱导结肠黏膜中的抗氧化能力。本文对此进行了广泛讨论。
