Jafari Seyyed Mehdi, Panjehpour Mojtaba, Aghaei Mahmoud, Joshaghani Hamid Reza, Enderami Seyed Ehsan
Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Cell Biochem. 2017 Sep;118(9):2909-2920. doi: 10.1002/jcb.25945. Epub 2017 May 3.
Numerous studies have demonstrated the role of A3 adenosine receptor (A3AR) and signaling pathways in the multiple aspects of the tumor. However, there is a little study about the function of A3AR in the biological processes of cancer stem cells (CSCs). CSCs have a critical role in the maintenance and survival of breast cancer. The aim of current study was to investigate the effect of A3AR agonist on breast cancer stem cells (BCSCs). XTT assay showed antiproliferative effect of A3AR agonist (Cl-IB-MECA) on BCSCs. Our results also demonstrated that A3AR agonist reduces mammosphere formation in a dose-dependent manner. Flow cytometry analysis showed that A3AR agonist induces G1 cell cycle arrest and apoptosis in BCSCs. Western blot assay showed that A3AR agonist inhibits the expression of cell cycle and apoptotic regulatory proteins as well as the expression of ERK1/2 and GLI-1 proteins. Finally, these findings propose that A3AR agonist induces cell cycle arrest and apoptosis in BCSCs by inhibition of ERK1/2 and GLI-1 cascade. J. Cell. Biochem. 118: 2909-2920, 2017. © 2017 Wiley Periodicals, Inc.
大量研究已证明A3腺苷受体（A3AR）及其信号通路在肿瘤的多个方面所起的作用。然而，关于A3AR在癌症干细胞（CSCs）生物学过程中的功能研究却很少。CSCs在乳腺癌的维持和存活中起着关键作用。本研究的目的是探究A3AR激动剂对乳腺癌干细胞（BCSCs）的影响。XTT分析显示A3AR激动剂（Cl-IB-MECA）对BCSCs具有抗增殖作用。我们的研究结果还表明，A3AR激动剂以剂量依赖的方式减少乳腺球的形成。流式细胞术分析显示，A3AR激动剂可诱导BCSCs的G1期细胞周期阻滞和凋亡。蛋白质免疫印迹分析表明，A3AR激动剂可抑制细胞周期和凋亡调节蛋白的表达，以及ERK1/2和GLI-1蛋白的表达。最后，这些研究结果表明，A3AR激动剂通过抑制ERK1/2和GLI-1级联反应诱导BCSCs的细胞周期阻滞和凋亡。《细胞生物化学杂志》118: 2909 - 2920, 2017。© 2017威利期刊公司
