Aquaporin-3 Inhibition Reduces the Growth of NSCLC Cells Induced by Hypoxia.

Background/Aims: Non-small cell lung cancer (NSCLC) is the leading cause of death worldwide. Although aquaporin-3 (AQP3) is widely distributed in mammalian tissues and over-expressed in NSCLC cells, there are limited studies on the effects of AQP3 knockdown on NSCLC cells under hypoxic conditions. Methods: The CCK-8 assay was used to calculate cell viability. Scratch-wound healing and transwell assays were used to detect cell migration and invasion. Apoptotic cells were measured by the TUNEL assay. mRNA expression levels were calculated via quantitative RT-PCR. Relative protein levels were determined by immunoblot assays. Results: AQP3 knockdown substantially reduced proliferation, migration, and invasion of A549 and NCl-H460 cells under hypoxic conditions. Moreover, AQP3 knockdown clearly induced cell apoptosis. Further analysis identified levels of HIF-1 alpha, VEGF, Raf, phosphor-MEK, and phosphor-ERK, whose activities were significantly attenuated in the AQP3 knockdown group. Conclusions: These findings indicate that AQP3 knockdown retards the growth of NSCLC cells partially through inhibiting HIF-1 alpha/VEGF and Raf/MEK/ERK signalling pathways. (C) 2016 The Author(s) Published by S. Karger AG, Basel