Menghua Wang, Zhe Wang, Naishuo Liu, Yujie Du, Yexue Ma, Shuqi Wang
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Structural analysis showed that CBP-4a was a novel pectin polysaccharide with a main chain composed of homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) domains. In vitro experiments indicated that CBP-4a could significantly enhance the sensitivity of HCT15 and CT26.WT cells to 5-FU in a non-cytotoxic manner; it could also enhance the S-phase arrest of the cell cycle, migration inhibition, ROS accumulation and apoptosis induced by 5-FU. In vivo experiments showed that the combination of CBP-4a and 5-FU significantly inhibited tumor growth in mice compared with 5-FU alone. 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引用次数: 0
摘要
结直肠癌(CRC)是全球第三大常见癌症。5-氟尿嘧啶(5-FU)是治疗结直肠癌的一线化疗药物;但其选择性差,副作用严重,长期使用容易产生耐药性。本研究采用超声辅助纤维素酶法提取枸杞多糖。在最佳提取条件下,粗多糖提取率最高可达14.34 ± 0.41 %,在此条件下可提取粗多糖(CBP)。从CBP中分离纯化了一种分子量为99.77 kDa的酸性均相多糖(CBP-4 A)。结构分析表明,CBP-4a是一种新型果胶多糖,其主链由均半乳糖醛酸(HG)和鼠李糖半乳糖醛酸- i (RG-I)结构域组成。体外实验表明,CBP-4a能显著提高HCT15和CT26的敏感性。WT细胞对5-FU无细胞毒性;还能增强5-FU诱导的细胞周期s期阻滞、迁移抑制、ROS积累和细胞凋亡。体内实验表明,与单独使用5-FU相比,CBP-4a与5-FU联合使用可显著抑制小鼠肿瘤生长。本研究扩大了C. baromez的用药范围,为开发辅助治疗结直肠癌的多糖药物提供了科学依据和理论支持。
The extraction optimization, characterization, and adjuvant therapeutic effects on colorectal cancer of a pectin polysaccharide (CBP-4 a) obtained from Cibotium barometz.
Colorectal cancer (CRC) is the third most common cancer worldwide. 5-fluorouracil (5-FU) is a first-line chemotherapeutic drug for the treatment of CRC; however, its selectivity is poor, it has serious side effects, and its long-term use is prone to drug resistance. In this study, the ultrasonic-assisted cellulase method was used to extract polysaccharides from Cibotium barometz. Under the optimum extraction conditions, the highest polysaccharide extraction rate reached 14.34 ± 0.41 %, and the crude polysaccharide of C. barometz (CBP) was extracted under these conditions. Furthermore, an acidic homogeneous polysaccharide (CBP-4 A) with a molecular weight of 99.77 kDa was isolated and purified from CBP. Structural analysis showed that CBP-4a was a novel pectin polysaccharide with a main chain composed of homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) domains. In vitro experiments indicated that CBP-4a could significantly enhance the sensitivity of HCT15 and CT26.WT cells to 5-FU in a non-cytotoxic manner; it could also enhance the S-phase arrest of the cell cycle, migration inhibition, ROS accumulation and apoptosis induced by 5-FU. In vivo experiments showed that the combination of CBP-4a and 5-FU significantly inhibited tumor growth in mice compared with 5-FU alone. This study expands the medicinal range of C. barometz and provides a scientific basis and theoretical support for the development of polysaccharide drugs for the adjuvant treatment of CRC.
期刊介绍:
The International Journal of Biological Macromolecules is a well-established international journal dedicated to research on the chemical and biological aspects of natural macromolecules. Focusing on proteins, macromolecular carbohydrates, glycoproteins, proteoglycans, lignins, biological poly-acids, and nucleic acids, the journal presents the latest findings in molecular structure, properties, biological activities, interactions, modifications, and functional properties. Papers must offer new and novel insights, encompassing related model systems, structural conformational studies, theoretical developments, and analytical techniques. Each paper is required to primarily focus on at least one named biological macromolecule, reflected in the title, abstract, and text.