Role of arachidonic acid metabolites in tumor growth inhibition by nonsteroidal antiinflammatory drugs.
OBJECTIVE
A murine model of squamous cell carcinoma (SCC) was used to determine the role of arachidonic acid (AA) metabolites in the growth of SCC of the head and neck.


METHODS
C3H/HeJ mice bearing SCC (SCC VII) were treated with cyclooxygenase inhibitors (piroxicam and nabumetone) or a 5-lipoxygenase inhibitor (ketoconazole). Growth curves were established, and final tumor weights were measured. Following sacrifice, tumor tissue homogenates were assayed for prostaglandin E2 (PGE2) and 12-hydroxyeicosatetraenoic acid (12-HETE) by enzyme-linked immunosorbent assay (ELISA), and leukotriene B4 (LTB4) by radioimmunoassay (RIA). Inflammatory cell infiltrate was assessed histologically.


RESULTS
A significant inhibition of tumor growth (P = .001) and final tumor weight (P = .002) was noted in mice treated with piroxicam and nabumetone. Inhibition of tumor growth was associated with increased tumor tissue levels of PGE2 (P = .04) and lymphocytic infiltration (P = .07). Significant inhibition of tumor growth (P = .002) and final tumor weight (P = .05) was also noted in mice treated with ketoconazole.


CONCLUSIONS
These data suggest that both cyclooxygenase and lipoxygenase metabolites of AA affect tumor growth in this model and that inhibition of tumor growth by inhibitors of AA metabolism may be caused by an enhanced inflammatory cell response at the tumor site.
Scioscia
K A
KA
Department of Otolaryngology, University of Pittsburgh School of Medicine, PA 15213, USA.
Snyderman
C H
CH
Rueger
R
R
Reddy
J
J
D'Amico
F
F
Comsa
S
S
Collins
B
B
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000032:analysis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002074:Butanones / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology*; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000032:analysis; D016859:Lipoxygenase Inhibitors; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D000077430:Nabumetone; D010894:Piroxicam / Q000494:pharmacology / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D010894:Piroxicam; D007975:Leukotriene B4; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D015232:Dinoprostone; D000077430:Nabumetone; D007654:Ketoconazole