Zou Pan, Yuan Shoujun, Yang Xin, Zhai Xingchen, Wang Jing
Department of Food Science and Engineering, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, No.73 Huanghe Road, Nangang District, Harbin, Heilongjiang Province 150090, PR China; Key Laboratory of Agro-product Quality and Safety, Institute of Quality Standard & Testing Technology for Agro-Product, Chinese Academy of Agricultural Sciences, Beijing 100081, PR China; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Haidian District, Beijing 100850, PR China.
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Haidian District, Beijing 100850, PR China.
Chem Biol Interact. 2018 Jan 5;279:129-135. doi: 10.1016/j.cbi.2017.11.010. Epub 2017 Nov 16.
Colon cancer is the third most common cancer, and yet there is a lack of effective therapeutic method with low side effects. Chitosan oligosaccharides (COS) is derived from chitosan after chitin deacetylation, and attracts more interests due to smaller molecular weight and soluble property. Previously, COS, mainly absorbed through intestinal epithelia, has been reported to exhibit many bioactivities, especially its anti-tumor effect. Recent references pay little attention to molecular weight distribution which is crucial for understanding its biological behavior. Here, we studied reducing sugar content and degree of polymerization (DP) of COS. 86.73% reducing sugar exists in COS sample and the content of chitosan fractions with 2-6 is 85.8%. COS suppressed the growth of HCT116 cells in vitro and in vivo, and the inhibition rate of tumor weight in vivo was high up to 58.6%. Moreover, the morphology observation, flow cytometry analysis and mRNA expression were applied to study the apoptosis related mechanism. COS treatment promoted mitosis, late stage apoptosis and S cell cycle arrest in HCT116 cells, and enhanced the mRNA expression of BAK and reduce BCL-2 and BCL-x. These findings may provide an important clue for clinical applications of COS as anti-tumor drug or pharmaceutic adjuvant in the future.
结肠癌是第三大常见癌症,但目前缺乏副作用小的有效治疗方法。壳寡糖(COS)是几丁质脱乙酰化后从壳聚糖衍生而来的,因其分子量较小且具有可溶性而备受关注。此前,COS主要通过肠上皮吸收,据报道具有多种生物活性,尤其是其抗肿瘤作用。近期的参考文献很少关注对理解其生物学行为至关重要的分子量分布。在此,我们研究了COS的还原糖含量和聚合度(DP)。COS样品中还原糖含量为86.73%,2-6聚糖部分的含量为85.8%。COS在体外和体内均抑制HCT116细胞的生长,体内肿瘤重量抑制率高达58.6%。此外,通过形态学观察、流式细胞术分析和mRNA表达来研究凋亡相关机制。COS处理促进HCT116细胞有丝分裂、晚期凋亡和S期细胞周期阻滞,并增强BAK的mRNA表达,降低BCL-2和BCL-x的表达。这些发现可能为未来COS作为抗肿瘤药物或药物佐剂的临床应用提供重要线索。