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

Abstract

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, À5 and À101C. The expression of AQP3 in response to freezing was determined using realtime 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 (Po0.001). 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 À101C (Po0.01). 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.

Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer

“…Xu and associates investigated the effect of AQP3 on matrix metalloproteinase in human gastric carcinoma cells and concluded that AQP3 may be a promising drug target [29]. In the field of urological neoplasms, Ismail et al provided evidence that prostate cancer cell lines in vitro become more sensitive to cryotherapy after inhibiting AQP3 by mercuric chloride and AQP3 siRNA [30]. …”

Can aquaporins be used as diagnostic and prognostic markers for uterine smooth muscle tumours?

“…Recently, it has been shown that AQP3 expression might be related to development of several carcinomas including gastric carcinoma [26,27], oesophageal and oral squamous cell carcinoma [28], cervical carcinoma [29] and cancers of the thyroid [30], pancreas [31], prostate [32,33], ovary [34] and skin [35,36]. In our study, AQP3 expression was observed in all tissue samples examined in LMS group except in one case.…”

Challenges and achievements in the therapeutic modulation of aquaporin functionality

“…AQP3 was further shown to facilitate growth of human esophageal and oral squamous cell carcinoma (Kusayama et al, 2011). In this context, downregulation of AQP3 by siRNA increased the therapeutic effect of cisplatin and led to higher sensitivity of prostate cancer cells to experimental cryotherapy (Ismail et al, 2009). …”