Aquaporin‐3 and aquaporin‐5 impact the development of pancreatic ductal adenocarcinoma spheroids

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related mortality, with poor survival due to late diagnosis and ineffective therapies. Aquaporin-3 (AQP3) and AQP5 are transmembrane proteins overexpressed in PDAC, promoting tumor progression and metastasis, representing promising therapeutic targets. Here, we investigated their involvement in PDAC spheroids' growth and morphology using two human PDAC cell lines, BxPC-3 and MiaPaca-2. Treatment with AQP3 inhibitors decreased spheroids' diameter, area, and viability and altered MiaPaca-2 spheroids' circularity, suggesting reduced growth. Similarly, silencing AQP3 or AQP5 in BxPC-3 spheroids decreased spheroids' size with a more pronounced viability reduction, indicating impaired growth and cell death. This study demonstrates, for the first time, the critical roles of AQP3 and AQP5 in PDAC spheroids' development.