School of Chinese Materia Medica, Beijing University of Chinese Medicine, 100029, Beijing, China.
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, 100700, Beijing, China.
Cell Death Dis. 2020 Sep 24;11(9):797. doi: 10.1038/s41419-020-02998-6.
Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.
多药耐药（MDR）是癌症化疗失败的主要挑战。磷脂酰肌醇 3-激酶（PI3K）是一种脂质激酶，可传播细胞内信号级联并调节多种细胞过程。PI3Ks 被认为是癌症治疗中化疗耐药的重要原因。蛋白激酶 B（AKT）也是 PI3K 信号的重要下游效应物，它调节多种途径，包括抑制细胞凋亡、刺激细胞生长和调节细胞代谢。本文综述了 PI3K/AKT 的异常激活作为调节 MDR 的关键环节。我们总结了与 PI3K/AKT 通路相关的众多主要靶点的调节，这与 MDR 进一步相关，包括凋亡相关蛋白的表达、ABC 转运和糖原合酶激酶-3β（GSK-3β）、与核因子 kappa beta（NF-κB）和哺乳动物雷帕霉素靶蛋白（mTOR）的协同作用，以及糖酵解的调节。
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