Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

Abstract

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.

Abrupt Regression of a Meningioma after Discontinuation of Cyproterone Treatment: Fig 1.

“…8 Despite evidence that antiprogesterone treatment reduces the size of meningioma, both in vitro and in vivo, such hormonotherapy is not part of the conservative management of meningioma. 9 Reports of spontaneous regression of meningiomas in the literature are rare. Apart from spontaneous resolution after intratumoral hemorrhage, 10 only 2 cases of regression have been reported in association with progestative hormonal treatment withdrawal.…”

Spontaneous Regression of an Asymptomatic Meningioma Associated With Discontinuation of Progesterone Agonist Administration -Case Report-

“…8) Administration of another antiprogesterone agent, onapristone, resulted in marked reduction of the meningioma size in both in vitro and in vivo studies. 16) However, no antiprogesterone therapies have been established yet for the treatment of meningiomas. 7) One study found that 63% of asymptomatic meningiomas did not exhibit tumor growth, and only 6% of all patients with lesions experienced symptoms during the observation period.…”

Orbita Nörojenik Tümörlerinin Klinik ve Tedavi Özellikleri

“…29 İn vitro ve in vivo deneylerde mifepristone (RU486) ve onapristone uygulamasının tümör hücrelerinin gelişimini inhibe ettiği ve tümör hacminde azalma sağladığı gösterilmiştir. 30 Cerrahi olarak çıkarılamayan menenjiomlu hastalara uygulanan mifepristone tedavisi sonrası tümörde regresyon tespit edilmiştir. 31 Schwannomlar genellikle izole olarak ortaya çıkan tümörlerdir.…”