MEMBRANE POTASSIUM CHANNELS AND HUMAN BLADDER-TUMOR CELLS - II - GROWTH-PROPERTIES

These experiments were done to determine the effect of glibenclamide a nd diazoxide on the growth of human bladder carcinoma (HTB-9) cells in vitro. Cell growth was assayed by cell counts, protein accumulation, and H-3-thymidine uptake. Glibenclamide added at 75 and 150 mu M for 4 8 hr reduced cell proliferation. Dose-inhibition curves showed that gl ibenclamide added for 48 hr reduced cell growth at concentrations as l ow as 1 mu M (IC50 = 73 mu M) when growth was assayed in the absence o f added serum. This mu M-effect on cell growth was in agreement with t he dose range in which glibenclamide decreased open probability of mem brane K-ATP channels. Addition of glibenclamide for 48 hr also altered the distribution of cells within stages of the cell cycle as determin ed by flow cytometry using 10(-5) M bromodeoxyuridine. Glibenclamide ( 100 mu M) increased the percentage of cells in G(0)/G(1) from 33.6% (v ehicle control) to 38.3% (P < 0.05), and it reduced the percentage of cells in S phase from 38.3% to 30.6%. On the other hand, diazoxide, wh ich opens membrane KA-rp channels in HTB-9 cells, stimulated growth me asured by protein accumulation, but it did not increase the cell numbe r. We conclude that the sulfonylurea receptor and the corresponding me mbrane K-ATP channel are involved in mechanisms controlling HTB-9 cell growth. However, K-ATP is not rate-limiting among the signaling mecha nisms or molecular switches that regulate the cell cycle.