BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. RESULTS: Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. CONCLUSION: Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.
BACKGROUND: Integrins are highly attractive targets in oncology due to their involvement in angiogenesis in a wide spectrum of cancer entities. Among several integrin inhibitors under clinical evaluation, cilengitide is the most promising compound. However, little is known about the cellular processes induced during cilengitide therapy in combination with irradiation and cisplatin in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: The cytostatic effect of cilengitide was assessed by proliferation assay in the three HNSCC cell lines SCC25, FaDu and CAL27. Combination experiments with cisplatin and irradiation were performed. Possible synergistic effects were calculated in combination index (CI) analyses. Colony forming inhibition was investigated in clonogenic assays. Real-time PCR arrays were used to evaluate target protein gene expression patterns. Flow cytometry was used to detect apoptosis. RESULTS: Used alone, cilengitide has only minor cytotoxic effects in HNSCC cell lines. However, combination with cisplatin resulted in synergistic growth inhibition in all three cell lines. Irradiation showed synergism in short-term experiments and in colony forming assays, an additive effect was detected. Real-time PCR assay detected downregulation of the antiapoptotic protein Bcl-2 after exposure of cells to cilengitide. CONCLUSION: Cilengitide in combination with cisplatin and irradiation may be a feasible option for the treatment of patients with head and neck cancer. However, further investigations are required to understand the exact mechanism that leads to synergistic cytotoxicity.
Authors: Ajjai Alva; Susan Slovin; Stephanie Daignault; Michael Carducci; Robert Dipaola; Ken Pienta; David Agus; Kathleen Cooney; Alice Chen; David C Smith; Maha Hussain Journal: Invest New Drugs Date: 2010-11-04 Impact factor: 3.850
Authors: Mark R Gilbert; John Kuhn; Kathleen R Lamborn; Frank Lieberman; Patrick Y Wen; Minesh Mehta; Timothy Cloughesy; Andrew B Lassman; Lisa M Deangelis; Susan Chang; Michael Prados Journal: J Neurooncol Date: 2011-07-08 Impact factor: 4.130
Authors: Tom Mikkelsen; Chaya Brodie; Susan Finniss; Michael E Berens; Jessica L Rennert; Kevin Nelson; Nancy Lemke; Stephen L Brown; Diane Hahn; Berend Neuteboom; Simon L Goodman Journal: Int J Cancer Date: 2009-06-01 Impact factor: 7.396
Authors: J B Vermorken; J Guigay; R Mesia; J M Trigo; U Keilholz; A Kerber; U Bethe; M Picard; T H Brummendorf Journal: Br J Cancer Date: 2011-05-03 Impact factor: 7.640
Authors: Tao Wang; Jiayi Huang; Mai Vue; Michael R Alavian; Hira Lal Goel; Dario C Altieri; Lucia R Languino; Thomas J FitzGerald Journal: Mol Cancer Res Date: 2018-09-28 Impact factor: 5.852
Authors: Hanadi Talal Ahmedah; Laurence H Patterson; Steven D Shnyder; Helen M Sheldrake Journal: Cancers (Basel) Date: 2017-05-26 Impact factor: 6.639