INHIBITORY EFFECTS OF CYCLOSPORINE-A ON RAT INSULINOMA CELL-PROLIFERATION, POLYAMINE CONTENT AND INSULIN-SECRETION

The effects of the immunosuppressive drug cyclosporin A on the growth and secretion of clonal rat insulinoma cells (RINm5F) was investigated in vitro. Particular attention was paid to the influence of cyclospor in A on the metabolism of polyamines, since these compounds have been implicated in regulation of the growth and function of insulin-produci ng cells. It was found that culture of the cells for 2 days in the pre sence of 0.1 mg/l of cyclosporin A failed to affect RINm5F cell prolif eration, polyamine content, cellular insulin content or secretion of i nsulin into the culture medium. When the concentration of cyclosporin A was raised to 1 mg/l, however, the growth rate and polyamine content of the cells were impeded in parallel with a decreased cellular insul in content and insulin secretion. Replenishment of the intracellular p olyamine content by addition of exogenous putrescine failed to prevent the decreased growth rate and insulin content, indicating that cyclos porin A does not exert its inhibitory effect on the growth and insulin content of the RINm5F primarily by decreasing the polyamine content o f these cells. Hence, cyclosporin A may be useful in decreasing the ra pid growth of insulin-producing tumor cells, but also impairs insulin secretion.