Treatment effect of buparlisib, cetuximab and irradiation in wild-type or PI3KCA-mutated head and neck cancer cell lines.
Invest New Drugs
; 33(2): 310-20, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25603975
ABSTRACT
Introduction In complement to anti-EGFR therapy, the targeting of PI3K/AKT/mTOR signaling pathway is of particular interest in the management of Head and Neck Squamous Cell Carcinoma (HNSCC). Here, we assess the effects of PI3K inhibition combined with anti-EGFR monoclonal antibody cetuximab and/or irradiation (RT). Material and methods Anti-proliferative effects of the combination of buparlisib (a specific PI3K inhibitor), cetuximab and RT was determined in two HNSCC cell lines (CAL33, PI3KCA H1047R-mutated and CAL27, PI3KCA wild-type). We examined biochemical factors related to proliferation, apoptosis (caspases), DNA repair (ERCC1, XRCC1) and the PI3K pathway (pEGFR/EGFR, pAKT/AKT, p-p70, p4EBP1). Results The best synergistic combined treatment in inhibiting cell proliferation was sequence 2 (cetuximab followed by buparlisib) in both cell lines. Addition of RT increased sequence 2 anti-proliferative effect only in CAL27. Data on protein expression indicated a possible activation of mTORC2 complex and caspases proteins in CAL27 not seen in CAL33. In CAL33, the synergistic anti-proliferative effect of the two drugs may derive from the higher sensitivity of mutated cells to PI3K targeting. Conclusions Our study demonstrates a synergistic effect of cetuximab followed by buparlisib in both PI3KCA wild-type and mutated cells, even with different intracellular signaling cross-talk depending on mutational status.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Morfolinas
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Fosfatidilinositol 3-Quinases
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Cetuximab
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Neoplasias de Cabeça e Pescoço
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Aminopiridinas
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Invest New Drugs
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA