CC-5079: a small molecule with MKP1, antiangiogenic, and antitumor activity
| Autor: | Steven K. Libutti, Peter H. Schafer, David I. Stirling, Mei He, Faribourz Payvandi, Sarah A. O'Connor, Huan N. Vu, Walter J. Miller, George W. Muller |
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| Rok vydání: | 2009 |
| Předmět: |
Umbilical Veins
Angiogenesis Angiogenesis Inhibitors Antineoplastic Agents Umbilical vein Chorioallantoic Membrane Gene Expression Regulation Enzymologic Mice In vivo Cell Movement Cell Line Tumor Nitriles medicine Animals Humans Lymphocytes Fibroblast Microvessel Aorta Chemistry Endothelial Cells Biological activity Dual Specificity Phosphatase 1 Fibroblasts In vitro Rats medicine.anatomical_structure Immunology Colonic Neoplasms Cancer research Surgery Chickens Ex vivo Cell Division |
| Zdroj: | The Journal of surgical research. 164(1) |
| ISSN: | 1095-8673 |
| Popis: | CC-5079, a small molecule inhibitor of tubulin polymerization and phosphodiesterase-4 activity, was evaluated for antiangiogenic and antitumor activities.First, CC-5079 in vitro activity on human umbilical vein endothelial cells (HUVECs), fibroblasts, and MC38 were evaluated by proliferation, migration, and invasion assays. Second, CC-5079 effect on microvessel formation was evaluated ex vivo by chick chorioallantoic membrane (CAM), rat aortic rings assays, and with directed in vivo angiogenesis assay (DIVAA). Third, CC-5079 antitumor effect was determined in treatment of C57BL/6 mice with MC38 tumors. Finally, CC-5079 modulation of MKP1 in HUVECs, human fibroblast, and MC38 were determined by RNA isolation for qRT-PCR.At the 0.1 μM concentration CC-5079 significantly inhibited HUVEC, fibroblast, and MC38 proliferation and migration (all P0.001). At the 0.1 μM concentration, CC-5079 also inhibited HUVEC invasion (P0.05) but not fibroblast. In the CAM and rat aortic ring assays, CC-5079 at 0.1 μM inhibited microvessel formation (P0.05). By DIVAA, CC-5079 at 1 mg/kg/d continuous delivered inhibited microvessel formation (P0.05). Intraperitoneal CC-5079 was well tolerated and inhibited the growth of subcutaneous MC38 at 100 mg/kg/d (P0.01). By qRT-PCR, CC-5079 stimulated MKP1 expression in HUVEC and fibroblast.CC-5079 demonstrated stimulation of MKP1, antiangiogenic, and antitumor properties. |
| Databáze: | OpenAIRE |
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