A36 Session 10: Adjunctive Therapeutic Approaches: Aquaporins: potential targets to enhance cryoablation

Aquaporins have been implicated in the angiogenesis of cancer cells whereby most cancer cells exhibit an increase in aquaporins. There is recent research activity to suggest that employing aquaporin channel blockers can slow the progress of cancer angiogenesis. A recent study by our group showed that increasing the number of aquaporin at the cell surface improved viability of the cells following a cryopreservation protocol. The thinking behind this study was that increasing the availability of aquaporins would improve water movement during freezing thus reducing the availability of water for intracellular ice formation leading to improved viability. In effect, the study attempted to manipulate and broaden the inverse–U curve of cell survival. Conversely, to enhance the effect of cryosurgery this group attempted to flatten the inverse–U curve by blocking the aquaporins with mercuric chloride ( HgCl 2 ) . By preventing water movement during freezing, the cells would exhibit higher incidence of intracellular formation and thus increase cell death. The goal of this study was to determine whether blocking aquaporins would lead to increased cell death at slower freezing rates and higher end temperatures which are typically seen at the boundary of the ice ball toward the end of a cryosurgical procedure. Preliminary experiments at a freezing rate of 1 °C/min and a holding temperature of −10 °C or −20 °C for 1, 5, and 15 min show that HgCl 2 treated cells had significant increase in cell death after thawing and 24 h incubation. Although much more studies needs to be conducted, this approach may prove to enhance the effectiveness in treating cancer with cryosurgery.