Regulation of Lewis lung carcinoma cell growth by prostaglandins
A cloned metastatic variant of a murine tumor cell line, Lewis lung carcinoma (LLC(C3), was synchronized by double exposure to thymidine (5 x 10-4 M) at G1/S boundary. The effects of Prostaglandin (PG)E1, PGE2, PG synthetase inhibitors, and an analog of cAMP (dbut-cANP) on the life cycle of synchronized LLC(C3) cells were examined. When added to cells in G1 phase, PGE1 and dbut-cAMP enhanced 3H-thymidine uptake during S phase. Both of these agents suppressed S phase when they were added to cells entering S phase. The addition of PGE2 to LLC(C3) cells in G1 phase had no effect on S phase of the synchronized LLC(C3) cells. Prostaglandin E2 suppressed S phase when it was added at the beginning of S phase. A low concentration of PGE2 was more suppressive to S phase than was a high concentration. Indomethacin, an irreversible PG synthetase inhibitor, and piroxicam, a reversible PG synthetase inhibitor, suppressed S phase of synchronized LLC(C3) cells. These results suggest that prostaglandins can regulate the cell cycle of LLC(C3) cells through modulation of cAMP levels.