Nonsteroidal antiinflammatory drugs and progestins synergistically enhance cell death in ovarian epithelial cells.
OBJECTIVE
There is growing evidence that progestins and nonsteroidal antiinflammatory drugs (NSAIDs) may prevent ovarian cancer. Because both induce apoptosis, we investigated the potential for synergistic impact of combined drug treatment on cell death.


METHODS
Using normal and malignant human ovarian epithelial cells and an NSAID-sensitive human colon cancer cell line, we evaluated the effects of progestins and NSAIDs alone and in combination on apoptosis.


RESULTS
Both progestins and NSAIDs dose dependently inhibited cell growth (P < .0001). Doses of NSAIDs or progestins that independently reduced cell viability by less than 30% synergistically reduced cell viability by 70-95% when combined. Similarly, the NSAID/progestin combination conferred 4- to 18-fold (P < .05) increased apoptosis over either treatment alone.


CONCLUSIONS
Our results suggest it may be possible to combine progestins and NSAIDs to achieve ovarian cancer prevention at lower doses of each than are required for single administration, thereby lessening the risk of side effects posed by these agents.
Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, IL 60201, USA. grodriguez@northshore.org
Gustavo C
GC
Rodriguez
Jane M
JM
Turbov
Andrew
A
Berchuck
M Sharon
MS
Stack
Jean A
JA
Hurteau
Larry G
LG
Thaete
Catherine P
CP
Barry
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000517:prevention & control*; D010053:Ovary / Q000187:drug effects* / Q000473:pathology*; D011372:Progestins / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011372:Progestins