PDF(Pubmed)
Abstract：
The rising incidence of colorectal cancer (CRC) and gastric cancer (GC) worldwide, coupled with the limited effectiveness of current chemotherapeutic agents, has prioritized the search for new therapeutic options. Natural substances, which often exhibit cytostatic properties, hold significant promise in this area. This review evaluates the anticancer properties of three natural alkaloids-berberine, sanguinarine, and chelerythrine-against CRC and GC. In vivo and in vitro studies have demonstrated that these substances can reduce tumor volume and inhibit the epithelial-mesenchymal transition (EMT) of tumors. At the molecular level, these alkaloids disrupt key signaling pathways in cancer cells, including mTOR, MAPK, EGFR, PI3K/AKT, and NF-κB. Additionally, they exhibit immunomodulatory effects, leading to the induction of programmed cell death through both apoptosis and autophagy. Notably, these substances have shown synergistic effects when combined with classical cytostatic agents such as cyclophosphamide, 5-fluorouracil, cetuximab, and erlotinib. Furthermore, berberine has demonstrated the ability to restore sensitivity in individuals originally resistant to cisplatin GC. Given these findings, natural compounds emerge as a promising option in the chemotherapy of malignant gastrointestinal tumors, particularly in cases with limited treatment options. However, more research is necessary to fully understand their therapeutic potential.
摘要：
全球结直肠癌(CRC)和胃癌(GC)的发病率不断上升,再加上目前化疗药物的疗效有限，优先考虑寻找新的治疗方案。天然物质,通常表现出细胞抑制特性，在这方面有很大的希望。本文综述了三种天然生物碱小檗碱的抗癌特性。血根碱,和白屈菜红碱-抗CRC和GC。体内和体外研究表明，这些物质可以减小肿瘤体积并抑制肿瘤的上皮-间质转化（EMT）。在分子水平上,这些生物碱破坏癌细胞的关键信号通路，包括mTOR,MAPK,EGFR,PI3K/AKT,和NF-κB。此外,它们表现出免疫调节作用，通过凋亡和自噬导致程序性细胞死亡的诱导。值得注意的是,这些物质与经典的细胞抑制剂如环磷酰胺组合时显示出协同作用，5-氟尿嘧啶,西妥昔单抗,还有厄洛替尼.此外，小檗碱已证明能够恢复最初对顺铂GC耐药的个体的敏感性。鉴于这些发现,天然化合物在恶性胃肠道肿瘤的化疗中成为一种有希望的选择，特别是在治疗选择有限的情况下。然而,更多的研究是必要的，以充分了解他们的治疗潜力。
