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Chemotherapy-Induced Apoptosis in Epithelial Ovarian Cancers

HAVRILESKY, LAURA J. BA; ELBENDARY, ALAA MD; HURTEAU, JEAN A. MD; WHITAKER, REGINA S. BS; RODRIGUEZ, GUSTAVO C. MD; BERCHUCK, ANDREW MD
Obstetrics & Gynecology: June 1995
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Objective To determine whether chemotherapy drugs elicit programmed cell death (apoptosis) in ovarian cancer cells.

Methods Monolayers of immortalized ovarian cancer cell lines and primary ovarian cancer cells obtained from ascites were grown in the presence of cisplatin, 4-hydroxyperoxycyclophosphamide (the active metabolite of cyclophospha-mide) or paclitaxel. Next, DNA was extracted from the cells and subjected to electrophoresis to determine if DNA laddering characteristic of apoptosis was present.

Results In three of six immortalized cell lines (OVCA 420, 429, and 433), apoptosis was not seen in response to any of the three drugs. In contrast, in OVCAR-3 and OVCA 432, DNA laddering consistent with apoptosis was observed in response to all three drugs. In the DOV 13 cell line, apoptosis was seen only with 4-hydroxyperoxycyclophosphamide. Among three primary ovarian cancers, cisplatin elicited apoptosis in one case. Both cell lines with mutant p53 genes (OVCAR-3 and OVCA 432) underwent apoptosis in response to all three drugs, whereas among three cell lines known to have normal p53 genes, one underwent apoptosis in response to 4-hydroxyperoxycyclophosphamide and two were unaffected.

Conclusion Ovarian cancer cell death in response to commonly used chemotherapeutic drugs involves the induction of a genetically programmed sequence of events (apoptosis) rather than simply necrosis.

Address reprint requests to: Andrew Berchuck, MD, Department of Obstetrics and Gynecology, Gynecologic Oncology, Duke University Medical Center, Box 3079, Durham, NC 27710.

© 1995 The American College of Obstetricians and Gynecologists