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通过激活 AMPK 靶向乳腺癌及其干细胞群体:新的见解。

Targeting Breast Cancer and Their Stem Cell Population through AMPK Activation: Novel Insights.

机构信息

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.

出版信息

Cells. 2022 Feb 7;11(3):576. doi: 10.3390/cells11030576.

Abstract

Despite some significant advancements, breast cancer has become the most prevalent cancer in the world. One of the main reasons for failure in treatment and metastasis has been attributed to the presence of cancer initiating cells-cancer stem cells. Consequently, research is now being focussed on targeting cancer cells along with their stem cell population. Non-oncology drugs are gaining increasing attention for their potent anticancer activities. Metformin, a drug commonly used to treat type 2 diabetes, is the best example in this regard. It exerts its therapeutic action by activating 5' adenosine monophosphate-activated protein kinase (AMPK). Activated AMPK subsequently phosphorylates and targets several cellular pathways involved in cell growth and proliferation and the maintenance of stem-like properties of cancer stem cells. Therefore, AMPK is emerging as a target of choice for developing effective anticancer drugs. Vanadium compounds are well-known PTP inhibitors and AMPK activators. They find extensive applications in treatment of diabetes and obesity via PTP1B inhibition and AMPK-mediated inhibition of adipogenesis. However, their role in targeting cancer stem cells has not been explored yet. This review is an attempt to establish the applications of insulin mimetic vanadium compounds for the treatment of breast cancer by AMPK activation and PTP1B inhibition pathways.

摘要

尽管取得了一些重大进展,但乳腺癌仍是全球最常见的癌症。治疗失败和转移的一个主要原因是癌症起始细胞-癌症干细胞的存在。因此,现在的研究重点是针对癌细胞及其干细胞群体。非肿瘤药物因其强大的抗癌活性而受到越来越多的关注。二甲双胍是一种常用于治疗 2 型糖尿病的药物,在这方面是最好的例子。它通过激活 5' 腺苷一磷酸激活蛋白激酶(AMPK)发挥其治疗作用。激活的 AMPK 随后磷酸化并靶向参与细胞生长和增殖以及维持癌症干细胞的干细胞样特性的几个细胞途径。因此,AMPK 作为开发有效抗癌药物的首选靶点而出现。钒化合物是众所周知的 PTP 抑制剂和 AMPK 激活剂。它们通过抑制 PTP1B 和 AMPK 介导的脂肪生成来广泛应用于糖尿病和肥胖症的治疗。然而,它们在靶向癌症干细胞方面的作用尚未得到探索。这篇综述试图通过 AMPK 激活和 PTP1B 抑制途径建立胰岛素模拟钒化合物在治疗乳腺癌中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca4d/8834477/2e4580029ede/cells-11-00576-g001.jpg

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