College of Chemistry and Molecular Sciences, Hubei Engineering Center of Natural Polymers-based Medical Materials, Wuhan University, Wuhan 430072, China.
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Carbohydr Polym. 2023 Sep 15;316:121069. doi: 10.1016/j.carbpol.2023.121069. Epub 2023 May 26.
Colorectal cancer is the third most common cancer in the world, and therapies with safety are in great need. In this study, the β-glucan isolated from Lentinus edodes was successfully fractionated into three fractions with different weight-average molecular weight (M) by ultrasonic degradation and used for the treatment of colorectal cancer. In our findings, the β-glucan was successfully degraded with the M decreased from 2.56 × 10 Da to 1.41 × 10 Da, exhibiting the triple helix structure without conformation disruption. The in vitro results indicate that β-glucan fractions inhibited colon cancer cell proliferation, induced colon cancer cell apoptosis, and reduced inflammation. The in vivo results based on Azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model demonstrate that the lower-molecular weight β-glucan fraction showed stronger anti-inflammatory and anti-colon cancer activities by reconstructing intestinal mucosal barrier, increasing short chain fatty acids (SCFAs) content, regulating metabolism of gut microbiota, and rebuilding the gut microbiota structure with the increased Bacteroides and the decreased Proteobacteria at the phylum level, as well as with the decreased Helicobacter and the increased Muribaculum at the genus level. These findings provide scientific basis for using the β-glucan to regulate gut microbiota as an alternative strategy in the clinical treatment of colon cancer.
结直肠癌是世界上第三大常见癌症,因此非常需要安全有效的治疗方法。在本研究中,通过超声降解成功地将从香菇中分离得到的β-葡聚糖分成了三个具有不同重均分子量(M)的级分,并用于结直肠癌的治疗。研究结果表明,β-葡聚糖成功降解,M 从 2.56×10 Da 降低至 1.41×10 Da,其仍保持三螺旋结构,未发生构象破坏。体外研究结果表明,β-葡聚糖级分可抑制结肠癌细胞增殖,诱导结肠癌细胞凋亡,并减少炎症。基于 AOM/葡聚糖硫酸钠(DSS)小鼠模型的体内研究结果表明,低分子量β-葡聚糖级分通过重建肠道黏膜屏障、增加短链脂肪酸(SCFAs)含量、调节肠道微生物群代谢以及重建肠道微生物群结构(厚壁菌门水平下的拟杆菌增加和变形菌门减少,以及属水平下的幽门螺杆菌减少和穆氏菌增加),表现出更强的抗炎和抗结肠癌活性,从而具有更强的抗炎和抗结肠癌活性。这些发现为使用β-葡聚糖作为调节肠道微生物群的替代策略来治疗结肠癌提供了科学依据。