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Aquaporin 3 knockdown suppresses tumour growth and angiogenesis in experimental non‐small cell lung cancer
Author(s) -
Xia Hui,
Ma YongFu,
Yu ChangHai,
Li YingJie,
Tang Jian,
Li JingBo,
Zhao YingNan,
Liu Yang
Publication year - 2014
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2014.078527
Subject(s) - gene knockdown , angiogenesis , cancer research , lung cancer , cell growth , aquaporin 1 , cancer , lung , cell , aquaporin , medicine , pathology , biology , microbiology and biotechnology , water channel , apoptosis , biochemistry , mechanical engineering , engineering , inlet
New FindingsWhat is the central question of this study? Aquaporins have been shown to play an important role in tumour development. It is not known whether short‐hairpin RNA targeting aquaporin 3 (AQP3) shows antitumour effects in experimental non‐small cell lung cancer (NSCLC).What is the main finding and its importance? Knockdown of AQP3 suppressed tumour growth and reduced angiogenesis in human NSCLS xenografts. Aquaporin 3 could thus be envisaged as a novel therapeutic target for NSCLC.Non‐small cell lung cancer (NSCLC) is one of the most common diseases encountered in medical oncology practice. The aim of the present study was to test the antitumour effects of short‐hairpin RNA targeting aquaporin 3 (AQP3) in experimental NSCLC. Expression of AQP3 was suppressed in human A549 and H1299 NSCLC cell lines by short‐hairpin RNA‐mediated silencing. Therapeutic effects were assessed by examining tumorigenicity using a subcutaneous xenograft mouse model of NSCLC. Aquaporin 3 knockdown inhibited tumour growth and prolonged survival of mice with tumours. Aquaporin 3 knockdown suppressed tumour proliferation, marked by enhanced expression of p53, an increased ratio of cleaved caspase 3 to pro‐caspase 3 and reduced expression of proliferating cell nuclear antigen and B‐cell lymphoma‐2 (bcl‐2). Aquaporin 3 knockdown inhibited tumour angiogenesis, marked by decreased CD31 immunostaining and reduced expression of hypoxia‐inducible factor‐2α and vascular endothelial growth factor. Aquaporin 3 knockdown reduced cellular glycerol content and suppressed mitochondrial ATP formation. Aquaporin 3 knockdown in vitro significantly suppressed activities of matrix metalloproteinases MMP2 and MMP9, reduced AKT phosphorylation and decreased cell invasiveness of A549 and H1299 cells. In conclusion, AQP3 knockdown suppressed tumour growth and reduced angiogenesis in human NSCLS xenografts. Aquaporin 3 could thus be envisaged as a novel therapeutic target for NSCLC.