Back to Search
Start Over
The efficacy and potential mechanisms of pyrotinib in targeting EGFR and HER2 in advanced oral squamous cell carcinoma.
- Source :
- BMC Oral Health; 8/6/2024, Vol. 24 Issue 1, p1-12, 12p
- Publication Year :
- 2024
-
Abstract
- Background: Human epidermal growth factor receptor 2 (HER2) plays an important role in the progression of multiple solid tumors and induces resistance to epidermal growth factor receptor (EGFR) target treatment. However, the expression status and the clinical significance of HER2 in oral squamous cell carcinoma (OSCC) is still controversial. Pyrotinib (PYR) is a promising novel EGFR/HER2 dual inhibitor, whose efficacy in OSCC has not been determined. Methods: 57 locally advanced de novo OSCC patients were included in this study to investigate the relationship between the HER2 expression levels and the prognosis by the tissue microarray analysis (TMA). In vitro and in vivo experiments were performed to retrieve the efficacy of PYR in OSCC. The main downstream of HER2 was evaluated by western blotting in OSCC cell lines and xenograft tumors to explore the potential mechanism of PYR. Results: This study revealed the primary tumor of OSCC had higher HER2 expression levels. Patients with HER2 overexpression had poor overall survival (P < 0.014) and poor disease free survival (P < 0.042). In vitro, PYR suppressed the proliferation, colony formation and migration of OSCC cells. It also promoted apoptosis of OSCC cells and induced cell cycle arrest. Furthermore, PYR was able to inhibit the occurrence and development of OSCC effectively in vivo. Western blotting revealed that PYR suppressed OSCC by inhibiting the phosphorylation of HER2, AKT and ERK. Conclusions: This study exhibited the anti-OSCC effects of PYR in vitro and in vivo, and demonstrated PYR inhibited OSCC cells by inducing apoptosis via the HER2/ AKT and ERK pathway. The result of this study also indicated locally advanced OSCC patients might benefit from HER2 assay and EGFR/HER2 dual inhibit treatment. [ABSTRACT FROM AUTHOR]
- Subjects :
- THERAPEUTIC use of antineoplastic agents
SQUAMOUS cell carcinoma
TISSUE arrays
IN vitro studies
WOUND healing
PEARSON correlation (Statistics)
MOUTH tumors
COLONY-forming units assay
PHOSPHORYLATION
T-test (Statistics)
DATA analysis
PROTEIN-tyrosine kinase inhibitors
CELL proliferation
APOPTOSIS
FISHER exact test
IN vivo studies
XENOGRAFTS
CELL motility
CELL cycle
CHI-squared test
MULTIVARIATE analysis
DESCRIPTIVE statistics
CELL lines
CELL culture
IMMUNOHISTOCHEMISTRY
KAPLAN-Meier estimator
LOG-rank test
DRUG efficacy
ANIMAL experimentation
WESTERN immunoblotting
ANALYSIS of variance
ONE-way analysis of variance
STATISTICS
PROGRESSION-free survival
DATA analysis software
EPIDERMAL growth factor receptors
DISEASE progression
OVERALL survival
REGRESSION analysis
Subjects
Details
- Language :
- English
- ISSN :
- 14726831
- Volume :
- 24
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- BMC Oral Health
- Publication Type :
- Academic Journal
- Accession number :
- 178855279
- Full Text :
- https://doi.org/10.1186/s12903-024-04459-4