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...

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Bibliographic Details
Published inOncology reports Vol. 19; no. 4; pp. 1039 - 1043
Main Authors TENTORI, Lucio, SUSANNA DORIO, Annalisa, MUZI, Alessia, MIGUEL LACAL, Pedro, RUFFINI, Federica, NAVARRA, Pierluigi, GRAZIANI, Grazia
Format Journal Article
LanguageEnglish
Published Athens S.n. 01.04.2008
Subjects
Animals
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Dacarbazine - analogs & derivatives
Dacarbazine - pharmacology
Dermatology
DNA Mismatch Repair
Drug Synergism
Endothelial Cells - drug effects
Integrins - antagonists & inhibitors
Male
Medical sciences
Melanoma - drug therapy
Melanoma - genetics
Melanoma - pathology
Mice
Mice, Inbred C57BL
Snake Venoms - pharmacology
Tumors
Tumors of the skin and soft tissue. Premalignant lesions
Antineoplastic agent
Peptides
Cell adhesion molecule
Malignant tumor
Biological activity
Alkylating agent
Cancerology
Integrin
Malignant melanoma
Cilengitide
Antagonist
Temozolomide
Cancer
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Summary: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.
ISSN:1021-335X
1791-2431
DOI:10.3892/or.19.4.1039