Effect of aspirin and indomethacin on prostaglandin E2 synthesis in C6 glioma cells.
Prostaglandin E2 (PGE2) plays an important role in immunosuppression and tumor growth. PGE2 inhibitors such as aspirin and indomethacin suppress experimental tumor growth. Little is known of the relationship between PGE2 synthesis in brain tumors and the dose of aspirin or indomethacin. The present study was undertaken to evaluate the effect of different doses of aspirin and indomethacin on PGE2 synthesis in C6 glioma cells. C6 glioma cells were incubated with different concentrations (2, 4, and 8 microM) of aspirin and indomethacin for 1, 2, 4, 6, 8, 12, and 24 hours. Intracellular PGE2 concentration was measured by enzyme immunoassay. Each concentration of aspirin and indomethacin effectively inhibited PGE2 synthesis. Concentrations of 2, 4, and 8 microM of aspirin significantly inhibited PGE2 production at 6, 4, and 1 hour, respectively, and the inhibition persisted for more than 24 hours (p < 0.05). Concentrations of 2 and 4 microM of indomethacin were effective at 4 and 2 hours (p < 0.05), respectively. However, inhibition was not observed beyond 12 hours (p > 0.05). Indomethacin 8 microM was effective at 1 hour and the inhibition persisted beyond 24 hours (p < 0.05). Our study demonstrates that aspirin and indomethacin inhibit PGE2 synthesis in C6 glioma cells and that low-dose aspirin is as effective as high-dose aspirin. This study may encourage future clinical use of low-dose aspirin in the prevention or treatment of brain tumors.
Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Shiuh-Lin
SL
Hwang
Kung-Shing
KS
Lee
Chih-Lung
CL
Lin
Ann-Shung
AS
Lieu
Chi-Yun
CY
Cheng
Joon-Khim
JK
Loh
Yan-Fen
YF
Hwang
Yu-Feng
YF
Su
Shen-Long
SL
Howng
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007213:Indomethacin / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone; D001241:Aspirin; D007213:Indomethacin