Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck
| Autor: | Cora Bucana, Samar A. Jasser, Maher N. Younes, Jeffrey N. Myers, Orhan G. Yigitbasi, Yasemin D. Yazici, Gordon B. Mills, Adel K. El-Naggar |
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| Rok vydání: | 2007 |
| Předmět: |
Pathology
medicine.medical_specialty Integrin Blotting Western Tetrazolium Salts Apoptosis Protein Serine-Threonine Kinases Cell Line Tumor medicine In Situ Nick-End Labeling Humans Integrin-linked kinase Phosphorylation biology Cell growth Kinase General Medicine medicine.disease Head and neck squamous-cell carcinoma Immunohistochemistry stomatognathic diseases Otorhinolaryngology Epidermoid carcinoma Cell culture Head and Neck Neoplasms embryonic structures Cancer research biology.protein Carcinoma Squamous Cell Surgery |
| Zdroj: | Archives of otolaryngology--headneck surgery. 133(1) |
| ISSN: | 0886-4470 |
| Popis: | Objective To study the expression of integrin-linked kinase (ILK) in human squamous cell carcinoma of the head and neck (SCCHN) tumor specimens and cell lines and the efficacy of the novel small molecule QLT0267. Design Immunohistochemical analysis of 17 SCCHN tumor tissue specimens and 3 normal tongue tissue specimens for ILK expression and in vitro analysis of the effectiveness of QLT0267 on SCCHN cells. Setting Academic medical center. Main Outcome Measures Expression levels of ILK in SCCHN tumor specimens and cell lines and the efficacy of QLT0267 in inhibiting cell growth and inducing apoptosis in SCCHN cell lines. Results Most SCCHN tumor specimens stained for ILK, whereas none of the 3 normal tongue tissue specimens stained for ILK. Integrin-linked kinase was expressed in all 6 SCCHN cell lines tested. In 4 pairs of normal and SCCHN tumor specimens, ILK expression and activity were higher in most tumor samples tested. A kinase assay showed that QLT0267 inhibited the ILK activity of 2 SCCHN cell lines (TU167 and MDA1986). Modified tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA fragmentation ladder, and TUNEL (terminal deoxynucleotidyl transferase–mediated biotin–deoxyuridine triphosphate nick-end labeling) assays showed that QLT0267 inhibited cell growth and induced apoptosis in these 2 cell lines. A dose-dependent decrease in Akt phosphorylation was observed for these 2 cell lines on treatment with QLT0267. Conclusions Integrin-linked kinase is overexpressed in SCCHN tumor specimens. Targeting ILK with the small-molecule ILK inhibitor QLT0267 inhibits cell growth and induces apoptosis in SCCHN cell lines by reducing ILK activity and Akt phosphorylation. Integrin-linked kinase may be an attractive target for molecular therapy with which to enhance treatment of SCCHN. |
| Databáze: | OpenAIRE |
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