Aquaporin water channels affect the response of conventional anticancer therapies of 3D grown breast cancer cells

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 chemo-therapies 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 over -expressing 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 chemother-apies is essential in advancing personalized medicine in breast carcinomas.

Automated summary

Aquaporin (AQP) water channels play a crucial role in the transport of water across cellular membranes and are associated with breast cancer. In vitro studies have shown that AQPs can influence the effectiveness of conventional anticancer chemotherapies. This study focused on AQP1, AQP3, and AQP5, which are often overexpressed in breast cancer, and evaluated their impact on the viability of breast cancer cell spheroids treated with different chemotherapies. The findings support the significant role of AQPs in the response to conventional chemotherapies and highlight the importance of understanding the individual proteins involved in resistance to chemotherapy for personalized medicine in breast cancer.