The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma.
Inhibitors of alphav integrins have been developed as anti-angiogenic agents for cancer therapy and, among them, cyclic RGD-containing pentapeptides, such as cilengitide, are the most commonly used integrin antagonists. In this study, cilengitide was tested in combination with the methylating agent temozolomide (TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic properties currently used for the therapy of metastatic melanoma. To this end, the influence of cilengitide and TMZ on malignant melanoma growth and endothelial cell proliferation were investigated, using in vitro and in vivo models. The results indicated that cilengitide and TMZ exerted synergistic antiproliferative effects against melanoma and endothelial cells in vitro and induced a statistically significant reduction of in vivo melanoma growth with respect to treatment with the methylating agent only. In conclusion, this study proposes the use of cilengitide in combination with TMZ for the treatment of metastatic melanoma, thereby opening novel perspectives for the use of integrin inhibitors to enhance the efficacy of chemotherapy.
Tentori
Lucio
L
Department of Neuroscience, University of Rome Tor Vergata, 00133 Rome, Italy.
Dorio
Annalisa Susanna
AS
Muzi
Alessia
A
Lacal
Pedro Miguel
PM
Ruffini
Federica
F
Navarra
Pierluigi
P
Graziani
Grazia
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D053843:DNA Mismatch Repair; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects; D016023:Integrins / Q000037:antagonists & inhibitors*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012910:Snake Venoms / Q000494:pharmacology*; D000077204:Temozolomide
D000970:Antineoplastic Agents; D016023:Integrins; D012910:Snake Venoms; C422910:Cilengitide; D003606:Dacarbazine; D000077204:Temozolomide