Zhang Xieyi, Liu Wangyang, Edaki Kazue, Nakazawa Yuta, Kamioka Hiroki, Fujita Atsushi, Onozato Ryoichi, Iijima Misa, Tsuchida Shigeru, Arai Takahiro, Fujita Yukiyoshi, Mizoi Kenta, Ogihara Takuo
Laboratory of Biopharmaceutics, Department of Pharmacology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-chou, Takasaki-shi, Gunma 370-0033, Japan.
Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare, 60 Nakaorui-chou, Takasaki-shi, Gunma 370-0033, Japan.
Can J Infect Dis Med Microbiol. 2021 Nov 28;2021:4005327. doi: 10.1155/2021/4005327. eCollection 2021.
Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.
肿瘤细胞药物外排活性增强导致的多药耐药（MDR）会严重影响抗肿瘤治疗的疗效。我们最近发现，与Snail转录调节因子激活相关的外排转运体P-糖蛋白（P-gp）活性增加可能主要由肺癌细胞中的埃兹蛋白（moesin）介导。在此，我们旨在系统评估临床肺癌和非癌样本中外排转运体（P-gp、乳腺癌耐药蛋白（BCRP）和多药耐药相关蛋白2（MRP2））、支架蛋白（埃兹rin（Ezr）、根蛋白（Rdx）和埃兹蛋白（Msn）；ERM蛋白）以及SNAI家族成员（Snail、Slug和Smac）的mRNA表达水平之间的关系。我们发现Snail与Msn、Msn与P-gp、Slug与MRP2以及Smuc与BCRP的相对（癌/非癌）mRNA表达水平之间存在高度相关性。这些发现支持了我们之前的结论，即Snail通过Msn调节P-gp活性，并进一步表明Slug和Smuc可能分别在肺癌细胞中对MRP2和BCRP的功能调节起作用。该试验已在UMIN000023923注册。
