Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck

Maher N. Younes, Orhan G. Yigitbasi, Yasemin D. Yazici, Samar A. Jasser, Cora D. Bucana, Adel K. El-Naggar, Gordon Mills, Jeffrey N. Myers

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)15-23
Number of pages9
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume133
Issue number1
DOIs
StatePublished - Jan 25 2007
Externally publishedYes

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Cell Line
Neoplasms
Apoptosis
Tumor Cell Line
Tongue
QLT 0267
Carcinoma, squamous cell of head and neck
integrin-linked kinase
Growth
Phosphorylation
Tetrazolium Salts
DNA Nucleotidylexotransferase
In Situ Nick-End Labeling
DNA Fragmentation
Biotin
Phosphotransferases
Outcome Assessment (Health Care)
Therapeutics

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology
  • Medicine(all)

Cite this

Younes, M. N., Yigitbasi, O. G., Yazici, Y. D., Jasser, S. A., Bucana, C. D., El-Naggar, A. K., ... Myers, J. N. (2007). Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck. Archives of Otolaryngology - Head and Neck Surgery, 133(1), 15-23. https://doi.org/10.1001/archotol.133.1.15

Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck. / Younes, Maher N.; Yigitbasi, Orhan G.; Yazici, Yasemin D.; Jasser, Samar A.; Bucana, Cora D.; El-Naggar, Adel K.; Mills, Gordon; Myers, Jeffrey N.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 133, No. 1, 25.01.2007, p. 15-23.

Research output: Contribution to journalArticle

Younes, Maher N. ; Yigitbasi, Orhan G. ; Yazici, Yasemin D. ; Jasser, Samar A. ; Bucana, Cora D. ; El-Naggar, Adel K. ; Mills, Gordon ; Myers, Jeffrey N. / Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell carcinoma of the head and neck. In: Archives of Otolaryngology - Head and Neck Surgery. 2007 ; Vol. 133, No. 1. pp. 15-23.
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AU - Yigitbasi, Orhan G.

AU - Yazici, Yasemin D.

AU - Jasser, Samar A.

AU - Bucana, Cora D.

AU - El-Naggar, Adel K.

AU - Mills, Gordon

AU - Myers, Jeffrey N.

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