DataSheet1_Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating β-Catenin Signaling and Intestinal Flora.docx

The first-line treatment for colorectal cancer (CRC) is 5-fluorouracil (5-FU). However, the efficacy of this treatment is sometimes limited owing to chemoresistance as well as treatment-associated intestinal mucositis and other adverse events. Growing evidence suggests that certain phytochemicals have therapeutic and cancer-preventing properties. Further, the synergistic interactions between many such plant-derived products and chemotherapeutic drugs have been linked to improved therapeutic efficacy. Polysaccharides extracted from Albuca bracteata (Thunb.) J.C.Manning and Goldblatt (ABP) have been reported to exhibit anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, murine CRC cells (CT26) and a murine model of CRC were used to examine the anti-tumor properties of ABP and explore the mechanism underlying the synergistic interactions between ABP and 5-FU. Our results revealed that ABP could inhibit tumor cell proliferation, invasion, and migratory activity in vitro and inhibited tumor progression in vivo by suppressing β-catenin signaling. Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone. Moreover, this combination therapy resulted in the specific enrichment of Ruminococcus, Anaerostipes, and Oscillospira in the intestinal microbiota and increased fecal short-chain fatty acid (SCFA) levels (acetic acid, propionic acid, and butyric acid). The improvement in the intestinal microbiota and the increase in beneficial SCFAs contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Together, these data suggest that ABP exhibits anti-neoplastic activity and can effectively enhance the efficacy of 5-FU in CRC treatment. Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.

结直肠癌（colorectal cancer, CRC）的一线治疗方案为5-氟尿嘧啶（5-fluorouracil, 5-FU）。然而，受化疗耐药、治疗相关性肠黏膜炎及其他不良事件影响，该疗法的疗效常受限。越来越多的研究证据表明，部分植物化学物具备治疗与防癌特性。此外，诸多此类植物来源产物与化疗药物间的协同相互作用，已被证实可提升治疗效能。

从Albuca bracteata (Thunb.) J.C.Manning and Goldblatt中提取的多糖（ABP），据报道具有抗氧化、抗炎及抗肿瘤活性。本研究采用小鼠结直肠癌细胞（CT26）与小鼠结直肠癌模型，探究ABP的抗肿瘤特性，并揭示ABP与5-FU协同作用的潜在分子机制。研究结果显示，ABP可在体外抑制肿瘤细胞的增殖、侵袭与迁移能力，并通过抑制β-连环蛋白（β-catenin）信号通路在体内延缓肿瘤进展。

此外，ABP与5-FU联合给药的治疗效果优于单一药物治疗。更重要的是，联合疗法可特异性富集肠道菌群中的瘤胃球菌属（Ruminococcus）、厌氧绳菌属（Anaerostipes）与颤螺菌属（Oscillospira），并提升粪便短链脂肪酸（short-chain fatty acid, SCFA）水平，包括乙酸、丙酸与丁酸。肠道菌群结构的改善与有益短链脂肪酸的增加，不仅增强了治疗效果，还减轻了5-FU带来的不良反应。

综上，上述数据表明ABP具备抗肿瘤活性，可有效提升5-FU在结直肠癌治疗中的疗效。因此，针对ABP在新型抗肿瘤药物及佐剂开发中的应用开展进一步研究具有重要意义，有望改善结直肠癌患者的临床预后。