本综述旨在总结生物碱作为 PI3K/Akt/mTOR (PAMT) 通路潜在调节剂在癌症治疗中的作用。 PAMT 通路在细胞生长、存活和代谢中发挥着关键作用，其失调会导致癌症特征。在健康细胞中，这条途径受到严格控制。然而，该通路在癌症中经常失调并变得异常活跃。这种情况的发生可能是由于途径本身的基因突变或其他因素造成的。这种慢性过度活动会促进癌症特征，例如不受控制的细胞分裂、细胞死亡抵抗力以及滋养肿瘤的血管形成增加。因此，PAMT 通路是癌症的重要治疗靶点。研究人员正在开发专门针对该通路不同组成部分的药物，旨在关闭它并减缓癌症进展。生物碱是植物中发现的一类天然存在的含氮分子，已成为潜在的治疗剂。这些生物碱可以针对 PAMT 通路中的不同点，抑制其活性，并可能导致癌细胞死亡或抑制肿瘤生长。正在进行研究探索各种生物碱在癌症治疗中的作用。小檗碱通过靶向 PAMT 通路降低 mTOR 活性并增加细胞凋亡，抑制癌细胞增殖。 Lycorine 抑制 Akt 磷酸化和 mTOR 激活，增加促凋亡蛋白的产生并降低细胞活力。在胶质母细胞瘤模型中，去氢骆驼蓬碱抑制 mTORC1。本综述重点关注吴茱萸碱、毛黄素、毛壳素 J、吲哚-3-甲醇、诺斯卡品、小檗碱、胡椒长明等生物碱，这些生物碱在靶向 PAMT 通路方面显示出前景。评估生物碱作为癌症治疗一部分的临床研究正在进行中，并且正在调查它们对患者结果的潜在影响。总之，生物碱代表了一种针对癌症中失调的 PAMT 通路的有前途的途径，并且有必要进行进一步的研究。版权所有 © 2024。由 Elsevier B.V. 出版。

This review aims to summarize the role of alkaloids as potential modulators of the PI3K/Akt/mTOR (PAMT) pathway in cancer therapy. The PAMT pathway plays a critical role in cell growth, survival, and metabolism, and its dysregulation contributes to cancer hallmarks. In healthy cells, this pathway is tightly controlled. However, this pathway is frequently dysregulated in cancers and becomes abnormally active. This can happen due to mutations in genes within the pathway itself or due to other factors. This chronic overactivity promotes cancer hallmarks such as uncontrolled cell division, resistance to cell death, and increased blood vessel formation to nourish the tumor. As a result, the PAMT pathway is a crucial therapeutic target for cancer. Researchers are developing drugs that specifically target different components of this pathway, aiming to turn it off and slow cancer progression. Alkaloids, a class of naturally occurring nitrogen-containing molecules found in plants, have emerged as potential therapeutic agents. These alkaloids can target different points within the PAMT pathway, inhibiting its activity and potentially resulting in cancer cell death or suppression of tumor growth. Research is ongoing to explore the role of various alkaloids in cancer treatment. Berberine reduces mTOR activity and increases apoptosis by targeting the PAMT pathway, inhibiting cancer cell proliferation. Lycorine inhibits Akt phosphorylation and mTOR activation, increasing pro-apoptotic protein production and decreasing cell viability. In glioblastoma models, harmine suppresses mTORC1. This review focuses on alkaloids such as evodiamine, hirsuteine, chaetocochin J, indole-3-carbinol, noscapine, berberine, piperlongumine, and so on, which have shown promise in targeting the PAMT pathway. Clinical studies evaluating alkaloids as part of cancer treatment are underway, and their potential impact on patient outcomes is being investigated. In summary, alkaloids represent a promising avenue for targeting the dysregulated PAMT pathway in cancer, and further research is warranted.Copyright © 2024. Published by Elsevier B.V.