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

Case report

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✓ 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 mifepristone 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.

Article Information

Address reprint requests to: Yasuhiro Matsuda, M.D., Department of Neurosurgery, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan.

© AANS, except where prohibited by US copyright law.

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Figures

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    Immunocytochemical studies for progesterone receptor (PR). × 215, counterstained with methyl green. A: Photomicrograph of a PR-positive meningioma obtained from Case 1, showing the presence of nuclear staining. B: Photomicrograph of a PR-negative meningioma obtained from Case 5, demonstrating the absence of nuclear and cytoplasmic staining.

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    Graphs showing the antitumor effect of antiprogesterones in the in vitro studies. Values show the mean ± standard error of the mean for four culture dishes. The mean values (growth) of optical density in the initial control were designated as 100%. Asterisks: significant difference from the comparable control, p < 0.05. Results are shown for PR-positive meningioma cells from Case 2 (upper) and for PR-negative meningioma cells from Case 7 (center) and Case 12 (lower).

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    Photomicrographs of a meningioma from Case 2. A: The original meningioma showing a typical whorl pattem. H & E, × 135. B and C: Meningioma cells grown in the subrenal capsule of the nude mouse. H & E, × 105 (B), × 260 (C). T = tumor; R = renal parenchyma.

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    Graphs showing the antitumor effect of antiprogesterones on three meningiomas implanted into the subrenal capsule of the nude mouse. The tumor volume is expressed as a percentage of control. The mean values of each tumor volume in controls were 1.314 cu mm (Case 2), 0.877 cu mm (Case 3), and 0.784 cu mm (Case 7). PR = progesterone receptor. Each column depicts the standard error of the mean of the tumor volume. The numbers within columns indicate the number of mice treated for 28 days with either vehicle alone (C), mifepristone (M), or onapristone (O). Asterisks: significant difference from the comparable control, p < 0.05.

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