ANTI-ANGIOGENIC DRUG AGM1470 SUPPRESSES SMOOTH-MUSCLE CELL-MIGRATION INDUCED BY ENDOTHELIAL PDGF

Objectives: To examine the effects of the anti-angiogenic drug AGM1470 on smooth muscle cell (SMC) migration activity stimulated by endothel ial cell (EC)-delived mitogen. Materials and Methods: Study 1; EC's we re cultured under pulsatile flow using MCDB151 medium. From the supern atant of these EC dishes we devised too types of conditioned medium; a nti-PDGF(+) containing 10 mu g/ml anti-PDGF antibody, and anti-PDGF(-) containing no antibody. SMC's were cultured using both media. Study 2 ; EC's were cultured under the same conditions using both types of med ium; A MCDB151 medium containing 10 ng/ml AGM1470, and MCDB151 medium alone. After the AGM1470 concentration had been adjusted to 10 ng/ml, SMC's were cultured using each medium; AGM-exposed EC and AGM-non-expo sed EC. SMC colony spreading distances were measured as an index of mi togenic activity for 4 days. Results: Study 1; the anti-PDGF(-) group showed an apparently greater spreading distance than the anti-PDGF(+) group. Study 2; the AGM-non-exposed EC group showed a significantly gr eater spreading distance than the AGM-exposed EC group. However, MTT a ssay revealed no differences in proliferation between the two groups. Conclusion: AGM1470 suppresses the EC production of this PDGF-like mit ogen as well as SMC migration activity.