The presence of the
progesterone receptor (PR) in
meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone
drug,
mifepristone, is a potent agent that inhibits the growth of cultured
meningioma cells and reduces the size of
meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of
mifepristone and a new potent antiprogesterone agent,
onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in
meningiomas in vitro and in vivo was also investigated.
Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study,
mifepristone and
onapristone exhibited
cytostatic and cytocidal effects against cultured
meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative
meningiomas showed no response to any dose of mifeprestone and/or
onapristone. In the in vivo arm,
meningioma cells, embedded in a
collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the
tumor volume regardless of the presence or absence of PR's. No histological changes in the
meningioma cells suggestive of
necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that
mifepristone and
onapristone have an antitumor effect against
meningioma cells via the PR's and/or another receptor, such as the
glucocorticoid receptor.