The tumour-inhibiting potential of the progesterone antagonist Onapristone in the human mammary carcinoma T61 in nude mice

The progesterone antagonist Onapristone proved to possess strong tumour-inhibiting activity in a panel of experimental mammary carcinomas. Its underlying mechanism of action is due to a progesterone-receptor-mediated induction of terminal differentiation and a specific blockade of the cell cycle and is also present in the absence of progesterone as was shown in the MXT mammary tumour. To prove this further, the tumour-inhibiting activity of Onapristone was investigated in the human postmenopausal T61 mammary tumour implanted in castrated male nude mice. Whereas Onapristone given alone had no effect on growth of established tumours, after stimulation of the relatively low progesterone receptor content of this tumour line with an oestrogen, Onapristone significantly inhibited tumour growth. Thus, we suggest that Onapristone exerts its antitumour action via progesterone receptors. As there is no endogenous progesterone in these mice, the tumour-inhibiting activity of Onapristone is not primarily due to a classical antihormonal effect.