C159
Expression of Eag1 and HERG potassium channels in ovarian cancer
Viren Asher1, Raheela Khan1, Heidi Sowter3, Robert Shaw1, Anish Bali2
1School of Graduate Entry Medicine and Health Sciences, Derby, UK, 2Derby Hospitals NHS Trust, Derby, UK, 3University of Derby, UK
Background
Ovarian cancer is the second most common cancer in the UK accounting for 6% of female deaths due to cancer. Potassium channels have been shown to be associated with various cancers playing a role in cell proliferation and progression and have generated interest as potential novel targets for tumour therapy.
Aim
To determine the expression of Eag1 and HERG potassium channels in ovarian cancer and to study their role in cell proliferation.
Method
The presence of Eag1 and HERG channels was studied in the human ovarian cancer cell line Skov-3, by immunofluorescence and in ovarian cancer tissue (following informed patient consent and ethics committee approval) by immunohistochemistry. The effect of voltage-gated potassium channel blockers on Skov-3 cell proliferation were also investigated using the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.
Results
Skov-3 cell lines demonstrated immunofluorescence in the presence of Eag1 and HERG antibody. There was also grade 3 staining of ovarian cancer tissue with both HERG and Eag1 antibody compared to grade 1 staining in normal ovarian tissue. Both 4-aminopyridine (4-AP) and tetraethylammonium (TEA), blockers of voltage-gated potassium channels, significantly (P<0.001) inhibited the proliferation of Skov-3 cells as measured by MTS assay. Skov-3 cell proliferation was also attenuated in the presence of the specific HERG channel blockers E4031 and Ergtoxin.
Conclusion
Eag1 and HERG channels are expressed in ovarian cancer. Potassium channel blockers have an inhibitory effect on proliferation of ovarian cancer cells with maximum effect at 96 hours of culture highlighting a potentially new therapeutic role in the treatment of ovarian cancer. Further to these results, we are presently using immunohistochemistry to demonstrate the presence of these channels in a cohort of 360 patients with ovarian cancer. We will correlate these results with the clinical and pathological parameters known to be important in the progression of ovarian cancer.
