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 NCI-H460 cells under hypoxic conditions. Moreover, AQP3 knockdown clearly induced cell apoptosis. Further analysis identified levels of HIF-1α, 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-1α/VEGF and Raf/MEK/ERK signalling pathways.
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 NCI-H460 cells under hypoxic conditions. Moreover, AQP3 knockdown clearly induced cell apoptosis. Further analysis identified levels of HIF-1α, 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-1α/VEGF and Raf/MEK/ERK signalling pathways.
Authors: Yohan Bossé; Zhonglin Li; Jun Xia; Venkata Manem; Robert Carreras-Torres; Aurélie Gabriel; Nathalie Gaudreault; Demetrius Albanes; Melinda C Aldrich; Angeline Andrew; Susanne Arnold; Heike Bickeböller; Stig E Bojesen; Paul Brennan; Hans Brunnstrom; Neil Caporaso; Chu Chen; David C Christiani; John K Field; Gary Goodman; Kjell Grankvist; Richard Houlston; Mattias Johansson; Mikael Johansson; Lambertus A Kiemeney; Stephen Lam; Maria T Landi; Philip Lazarus; Loic Le Marchand; Geoffrey Liu; Olle Melander; Gadi Rennert; Angela Risch; Susan M Rosenberg; Matthew B Schabath; Sanjay Shete; Zhuoyi Song; Victoria L Stevens; Adonina Tardon; H-Erich Wichmann; Penella Woll; Shan Zienolddiny; Ma'en Obeidat; Wim Timens; Rayjean J Hung; Philippe Joubert; Christopher I Amos; James D McKay Journal: Int J Cancer Date: 2019-12-09 Impact factor: 7.396