INHIBITORY EFFECTS OF UBENIMEX (BESTATIN) ON THE INVASION OF UTERINE CERVICAL-CARCINOMA CELLS AND THEIR PRODUCTION AND ACTIVATION OF GELATINASE-A

The present study was undertaken to investigate the effects of the ami nopeptidase inhibitor ubenimex (bestatin) on the invasive activity of cultured human uterine cervical carcinoma cells. The invasion of squam ous cell carcinoma OMC-1 and SKG-IIIb cells, and adeno-carcinoma OMC-4 and CAC-1 cells into reconstituted basement membrane (Matrigel) was i nhibited by the presence of bestatin in a concentration-dependent mann er. However, bestatin did not have any effect on tumor cell proliferat ion or migration. Immunoblot analysis of tumor-conditioned medium show ed that the treatment of tumor cells with bestatin resulted in the red uction of the 72 kDa gelatinase level (gelatinase A, latent form) in t he four cell lines examined, and the reduction of the 68 kDa gelatinas e level (gelatinase A, active form) in SKG-IIIb cells. Bestatin inhibi ted hydrolyzing activities towards substrates of aminopeptidases in tu mor cells, but did not directly inhibit gelatinase A. These results su ggest that bestatin may inhibit the invasion of uterine cervical carci noma cells possibly through the inhibitory mechanisms for production a nd activation of gelatinase A modulated by tumor aminopeptidases.