Irinotecan: a potential new chemotherapeutic agent for atypical or malignant meningiomas.
OBJECTIVE
There is currently no effective chemotherapy for meningiomas. Although most meningiomas are treated surgically, atypical or malignant meningiomas and surgically inaccessible meningiomas may not be removed completely. The authors have investigated the effects of the topoisomerase I inhibitor irinotecan (CPT-11) on primary meningioma cultures and a malignant meningioma cell line in vitro and in vivo.


METHODS
The effects of irinotecan on cellular proliferation in primary meningioma cultures and the IOMM-Lee malignant meningioma cell line were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry. Apoptosis following drug treatment was evaluated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and the DNA laddering assays. The effects of irinotecan in vivo on a meningioma model were determined with a subcutaneous murine tumor model using the IOMM-Lee cell line. Irinotecan induced a dose-dependent antiproliferative effect with subsequent apoptosis in the primary meningioma cultures (at doses up to 100 microM) as well as in the IOMM-Lee human malignant meningioma cell line (at doses up to 20 microM) irinotecan. In the animal model, irinotecan treatment led to a statistically significant decrease in tumor growth that was accompanied by a decrease in Bcl-2 and survivin levels and an increase in apoptotic cell death.


CONCLUSIONS
Irinotecan demonstrated growth-inhibitory effects in meningiomas both in vitro and in vivo. Irinotecan was much more effective against the malignant meningioma cell line than against primary meningioma cultures. Therefore, this drug may have an important therapeutic role in the treatment of atypical or malignant meningiomas and should be evaluated further for this purpose.
Gupta
Vinay
V
Department of Pathology, University of Southern California, Los Angeles, California 90089, USA.
Su
Yuzhuang S
YS
Samuelson
Christian G
CG
Liebes
Leonard F
LF
Chamberlain
Marc C
MC
Hofman
Florence M
FM
Schönthal
Axel H
AH
Chen
Thomas C
TC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000077146:Irinotecan; D008297:Male; D008579:Meningioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D040521:Subcutaneous Tissue
D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D000077146:Irinotecan; D002166:Camptothecin