Abstract：
Aquaporin (AQP) water channels facilitate water transport across cellular membranes and are essential in regulation of body water balance. Moreover, several AQPs are overexpressed or ectopically expressed in breast cancer. Interestingly, several in vitro studies have suggested that AQPs can affect the response to conventional anticancer chemotherapies. Therefore, we took a systematic approach to test how AQP1, AQP3 and AQP5, which are often over-/ectopically expressed in breast cancer, affect total viability of 3-dimensional (3D) breast cancer cell spheroids when treated with the conventional anticancer chemotherapies Cisplatin, 5-Fluorouracil (5-FU) and Doxorubicin, a Combination of the three drugs as well as the Combination plus the Ras inhibitor Salirasib. Total viability of spheroids overexpressing AQP1 were decreased by all treatments except for 5-FU, which increased total viability by 20% compared to DMSO treated controls. All treatments reduced viability of spheroids overexpressing AQP3. In contrast, only Doxorubicin, Combination and Combination + Salirasib reduced total viability of spheroids overexpressing AQP5. Thus, this study supports a significant role of AQPs in the response to conventional chemotherapies. Evaluating the role of individual proteins that contribute to resistance to chemotherapies is essential in advancing personalized medicine in breast carcinomas.
摘要：
水通道蛋白（AQP）水通道促进水跨细胞膜的运输，在调节体内水平衡方面至关重要。此外，一些AQP在乳腺癌中过度表达或异位表达。有趣的是,多项体外研究表明,AQP可以影响对常规抗癌化疗的反应.因此,我们采取了系统的方法来测试AQP1，AQP3和AQP5如何在乳腺癌中过度/异位表达，用常规抗癌化疗顺铂治疗时，会影响三维（3D）乳腺癌细胞球体的总活力，5-氟尿嘧啶（5-FU）和阿霉素，三种药物的组合以及组合加Ras抑制剂Salirasib。除5-FU外，所有处理均降低了过表达AQP1的球体的总生存力，与DMSO处理的对照相比,其增加了20%的总活力。所有处理均降低过表达AQP3的球状体的活力。相比之下,只有阿霉素,组合和组合+Salirasib降低了过表达AQP5的球体的总活力。因此，本研究支持AQPs在常规化疗应答中的重要作用.评估导致化疗耐药的单个蛋白质的作用对于推进乳腺癌个性化医疗至关重要。
