Macao Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR 999078, China.
Molecules. 2023 Jan 11;28(2):740. doi: 10.3390/molecules28020740.
Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5'-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the "Warburg effect" via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (-)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.
乳腺癌是全球女性中常见的癌症。现有的临床治疗策略已经能够限制乳腺癌的进展和癌症转移，但涉及多个调节剂的异常代谢、免疫抑制和多药耐药仍然是乳腺癌治疗的主要挑战。腺苷 5'-单磷酸 (AMP)-激活蛋白激酶 (AMPK) 可以通过乳腺癌中的多种代谢信号通路调节代谢重编程并逆转“Warburg 效应”。先前的研究表明，AMPK 的激活抑制了乳腺癌细胞的生长和转移，并刺激了免疫细胞的反应。然而，其他一些报告称，乳腺癌的发展和不良预后与 AMPK 的过表达和异常激活有关。因此，AMPK 在乳腺癌进展中的作用仍存在争议。在这篇综述中，我们总结了 AMPK 的现有认识，特别是 AMPK 在癌症进展中的全面双向作用；讨论了 AMPK 的药理学激活剂和一些特定分子，包括影响这些激活剂在癌症治疗中疗效的天然产物（包括小檗碱、姜黄素、(-)-表没食子儿茶素-3-没食子酸酯、人参皂苷和紫杉醇）；并详细阐述了 AMPK 作为治疗乳腺癌的潜在治疗靶点的作用。
