Abstract
Recently improved understanding of the pathogenesis of human head and neck squamous cell carcinoma (HNSCC) has led to the development of new, molecular-based therapeutic strategies, one of the more promising is the utilisation of tyrosine kinase (TK) inhibitors, targeting epidermal growth factor receptor (EGFR). In this study, we tested for gefitinib effectiveness in a broad panel of 12 newly established HNSCC cell lines, investigating its ability to reduce cell growth, to induce apoptosis and to modulate cell cycle and various EGFR pathway-related targets. Gefitinib IC50 values ranged between 0.064 and 33 μM, its capability to induce apoptosis and cell accumulation in G0/G1 phase was cell line-specific, and the main EGFR-related pathway involved in gefitinib activity was PI3K/Akt/mTor. We characterised our in vitro panel extensively, with the aim to identify predictive factors for gefitinib effectiveness; all cell lines were free of human papillomavirus infection, two were positive for Fhit expression, four expressed wild-type p53, and all of them variously expressed the other two p53 family members, p63 and p73. The comparison between the targets analysed and gefitinib effectiveness evidenced the absence of a clear relationship, excluding them as predictive factors for gefitinib efficacy. Our results confirmed the in vitro efficacy of an anti-EGFR approach, but other targets than those analysed here should be characterised in order to identify valid predictive factors for gefitinib utilisation.
| Original language | English |
|---|---|
| Pages (from-to) | 809-817 |
| Number of pages | 9 |
| Journal | International Journal of Molecular Medicine |
| Volume | 21 |
| Issue number | 6 |
| Publication status | Published - Jun 2008 |
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Keywords
- Gefitinib sensitivity
- Head and neck squamous carcinoma cell lines
- Molecular characterization
ASJC Scopus subject areas
- Genetics
Cite this
Validation of gefitinib effectiveness in a broad panel of head and neck squamous carcinoma cells. / Sebastian, S.; Azzariti, Amalia; Accardi, R.; Conti, D.; Pilato, B.; Lacalamita, R.; Porcelli, L.; Simone, G. M.; Tommasi, S.; Tommasino, M.; Paradiso, A.
In: International Journal of Molecular Medicine, Vol. 21, No. 6, 06.2008, p. 809-817.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Validation of gefitinib effectiveness in a broad panel of head and neck squamous carcinoma cells
AU - Sebastian, S.
AU - Azzariti, Amalia
AU - Accardi, R.
AU - Conti, D.
AU - Pilato, B.
AU - Lacalamita, R.
AU - Porcelli, L.
AU - Simone, G. M.
AU - Tommasi, S.
AU - Tommasino, M.
AU - Paradiso, A.
PY - 2008/6
Y1 - 2008/6
N2 - Recently improved understanding of the pathogenesis of human head and neck squamous cell carcinoma (HNSCC) has led to the development of new, molecular-based therapeutic strategies, one of the more promising is the utilisation of tyrosine kinase (TK) inhibitors, targeting epidermal growth factor receptor (EGFR). In this study, we tested for gefitinib effectiveness in a broad panel of 12 newly established HNSCC cell lines, investigating its ability to reduce cell growth, to induce apoptosis and to modulate cell cycle and various EGFR pathway-related targets. Gefitinib IC50 values ranged between 0.064 and 33 μM, its capability to induce apoptosis and cell accumulation in G0/G1 phase was cell line-specific, and the main EGFR-related pathway involved in gefitinib activity was PI3K/Akt/mTor. We characterised our in vitro panel extensively, with the aim to identify predictive factors for gefitinib effectiveness; all cell lines were free of human papillomavirus infection, two were positive for Fhit expression, four expressed wild-type p53, and all of them variously expressed the other two p53 family members, p63 and p73. The comparison between the targets analysed and gefitinib effectiveness evidenced the absence of a clear relationship, excluding them as predictive factors for gefitinib efficacy. Our results confirmed the in vitro efficacy of an anti-EGFR approach, but other targets than those analysed here should be characterised in order to identify valid predictive factors for gefitinib utilisation.
AB - Recently improved understanding of the pathogenesis of human head and neck squamous cell carcinoma (HNSCC) has led to the development of new, molecular-based therapeutic strategies, one of the more promising is the utilisation of tyrosine kinase (TK) inhibitors, targeting epidermal growth factor receptor (EGFR). In this study, we tested for gefitinib effectiveness in a broad panel of 12 newly established HNSCC cell lines, investigating its ability to reduce cell growth, to induce apoptosis and to modulate cell cycle and various EGFR pathway-related targets. Gefitinib IC50 values ranged between 0.064 and 33 μM, its capability to induce apoptosis and cell accumulation in G0/G1 phase was cell line-specific, and the main EGFR-related pathway involved in gefitinib activity was PI3K/Akt/mTor. We characterised our in vitro panel extensively, with the aim to identify predictive factors for gefitinib effectiveness; all cell lines were free of human papillomavirus infection, two were positive for Fhit expression, four expressed wild-type p53, and all of them variously expressed the other two p53 family members, p63 and p73. The comparison between the targets analysed and gefitinib effectiveness evidenced the absence of a clear relationship, excluding them as predictive factors for gefitinib efficacy. Our results confirmed the in vitro efficacy of an anti-EGFR approach, but other targets than those analysed here should be characterised in order to identify valid predictive factors for gefitinib utilisation.
KW - Gefitinib sensitivity
KW - Head and neck squamous carcinoma cell lines
KW - Molecular characterization
UR - http://www.scopus.com/inward/record.url?scp=47649117616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47649117616&partnerID=8YFLogxK
M3 - Article
VL - 21
SP - 809
EP - 817
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 6
ER -