Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey; Graduate School of Natural and Applied Sciences, Yeditepe University, Istanbul, Turkey; Department of Neuropharmacology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey; Graduate School of Natural and Applied Sciences, Yeditepe University, Istanbul, Turkey.
Gene. 2023 Jun 30;871:147425. doi: 10.1016/j.gene.2023.147425. Epub 2023 Apr 11.
Prostate cancer (PCa) is the second most diagnosed cancer in males. Understanding the molecular mechanism and investigation of novel ways to block PCa growth or metastasis are vital and a medical necessity. In this study, we examined differential expression of MEIS1/2/3 and its associated factors in PCa cell lines. MEIS1/2/3 content, reactive oxygen species, and cell cycle status were analyzed in PCa cells post MEIS inhibitor (MEISi) treatments, which is developed in our laboratory as a first-in-class small molecule inhibitor. A correlation was detected between MEIS content and MEISi IC50 values of PCa cells. MEISi decreased the viability of PC-3, DU145, 22Rv-1 and LNCaP cells, and significantly increased apoptosis in parallel with the increased cellular ROS content. The efficacy of MEISi was shown to positively correlate with the levels of MEIS1/2/3 proteins and the long term exposure to MEISi elevated MEIS1/2/3 protein content in PCa cells. Our findings suggest that MEISi could be used to target PCa with high MEIS expression in order to reduce PCa viability and growth; however, more research is needed before this can be translated into clinical settings.
前列腺癌（PCa）是男性中第二大常见的癌症。了解其分子机制并探索新型方法来阻止 PCa 的生长或转移至关重要，这是医学的必要需求。在这项研究中，我们研究了 MEIS1/2/3 的差异表达及其在前列腺癌细胞系中的相关因素。我们分析了前列腺癌细胞中 MEIS 抑制剂（MEISi）处理后 MEIS1/2/3 的含量、活性氧和细胞周期状态，该 MEISi 是我们实验室开发的一种首创的小分子抑制剂。我们检测到 MEIS 含量与前列腺癌细胞 MEISi IC50 值之间存在相关性。MEISi 降低了 PC-3、DU145、22Rv-1 和 LNCaP 细胞的活力，并随着细胞 ROS 含量的增加，细胞凋亡显著增加。MEISi 的疗效与 MEIS1/2/3 蛋白水平呈正相关，长期暴露于 MEISi 会增加前列腺癌细胞中 MEIS1/2/3 蛋白的含量。我们的研究结果表明，MEISi 可以用于靶向高 MEIS 表达的前列腺癌，以降低前列腺癌的活力和生长；然而，在将其转化为临床应用之前，还需要进行更多的研究。
