Differential modulation of PI3K/Akt/mTOR activity by EGFR inhibitors: A rationale for co-targeting EGFR and PI3K in cisplatin-resistant HNSCC.
Head Neck
; 46(5): 1126-1135, 2024 05.
Article
in En
| MEDLINE
| ID: mdl-38429897
ABSTRACT
PURPOSE:
To find a new strategy to treat cisplatin-resistant head and neck squamous cell carcinoma (HNSCC), we investigated the effects of EGFR inhibitors on the PI3K/Akt/mTOR pathway and determined the efficacy of EGFR inhibitors in combination with PI3K inhibitors to suppress cell proliferation in cisplatin-resistant-HNSCC.METHODS:
The cisplatin-resistant HNSCC cell lines were treated with four FDA approved EGFR inhibitors, which included Gefitinb or Erlotinib alone, or in combination with the pan-PI3K inhibitor, BKM120. Phosphorylation and total protein levels of cells were assessed by Western blot analysis. Cell proliferation was examined by MTS assay. Apoptosis was analyzed by flow cytometry.RESULTS:
Cisplatin-resistant HNSCC cells were also resistant to EGFR inhibitors. However, a combination of EGFR inhibitors with PI3K inhibitor BKM120 dramatically improved the efficacy of EGFR inhibitors to inhibit cell proliferation and induce apoptosis. Furthermore, treatment with EGFR inhibitors differentially affected the phosphorylation of Akt and mTOR, which included partial inhibition, no inhibition, and induction. A combination of EGFR inhibitors and BKM120 completely blocked phosphorylation of EGFR, Akt, and S6K (an mTOR target).CONCLUSION:
Our data provided a rationale for EGFR inhibitors in combination with PI3K inhibitors to treat cisplatin-resistant HNSCC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Morpholines
/
Cisplatin
/
Head and Neck Neoplasms
/
Aminopyridines
Limits:
Humans
Language:
En
Journal:
Head & neck
/
Head Neck
/
Head neck
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States