Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy

• Published in: British journal of cancer Vol. 100; no. 12; pp. 1889 - 1895
• Main Authors: Ismail, M, Bokaee, S, Davies, J, Harrington, K J, Pandha, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.06.2009; Nature Publishing Group
• Subjects: Ablation; Aquaporin 3 - antagonists & inhibitors; Aquaporin 3 - metabolism; Aquaporins; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Cell Line, Tumor; Cell Membrane - metabolism; Cell Survival; Colorectal cancer; Cryotherapy; Drug Resistance; Epidemiology; Fluorescent Antibody Technique; Humans; Kinases; Male; Medical research; Medical sciences; Mercuric Chloride - pharmacology; Molecular Medicine; Nephrology. Urinary tract diseases; Oncology; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - physiology; Solute movement; Temperature; Translational Therapeutics; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United Kingdom > UK; AQP3; prostate cancer; cryotherapy; Water; Urinary system disease; Prostate disease; Ionic channel; Malignant tumor; Sensitivity; Cancerology; Treatment; Inhibitor; Male genital diseases; Prostate cancer; Cryotherapy; Aquaporin; Tumor cell; Carrier protein; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605093

Aquaporins ( AQPs ) are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. In this study, we investigate the role of inhibiting AQPs in sensitising prostate cancer cells to cryotherapy. PC-3 and DU145 prostate cancer cells were cooled to 0, −5 and −10°C. The expression of AQP3 in response to freezing was determined using real-time quantitative polymerase chain reaction (RT–qPCR) and western blot analysis. Aquaporins were inhibited using mercuric chloride (HgCl 2 ) and small interfering RNA (siRNA) duplex, and cell survival was assessed using a colorimetric assay. There was a significant increase in AQP3 expression in response to freezing. Cells treated with AQP3 siRNA were more sensitive to cryoinjury compared with control cells ( P <0.001). Inhibition of the AQPs by HgCl 2 also increased the sensitivity of both cell lines to cryoinjury and there was a complete loss of cell viability at −10°C ( P <0.01). In conclusion, we have shown that AQP3 is involved directly in cryoinjury. Inhibition of AQP3 increases the sensitivity of prostate cancer cells to freezing. This strategy may be exploited in the clinic to improve the efficacy of prostate cryotherapy.