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Celecoxib inhibits insulin-like growth factor 1 induced growth and invasion in non-small cell lung cancer
Chen-Hui Liu1, Hong-Guang Bao, Ya-Li Ge
1Departments of Anesthesiology, Affiliated Nanjing Hospital of Nanjing Medical University, Nanjing 210006, P.R. China.
Abstract:
Despite a large number of studies indicating that celecoxib plays an important role in the prevention and treatment of tumors, the detailed molecular mechanisms are not well understood. The aim of the present study was to investigate the effect of celecoxib on insulin-like growth factor 1 (IGF-1)-induced growth and invasion in non-small cell lung cancer (NSCLC). For these experiments, IGF-1-induced cell growth and invasion were analyzed in A549 cells in the presence and absence of celecoxib. The effects of celecoxib on the expression of phosphorylated type-1 IGF receptor (IGF-1R) and phosphorylated AKT (p-AKT) were examined using western blot analysis. The influence of celecoxib on IGF-binding protein-3 (IGFBP-3) expression was analyzed using ELISA. Celecoxib inhibited IGF-1-stimulated growth and invasion in a dose-dependent manner. Celecoxib also reduced the expression of IGF-1R, IGFBP-3 and phosphorylation of AKT. The results suggest that modulating the IGF axis may be a new mechanism for the anticancer effect of celecoxib on NSCLC.
Insights
Celecoxib hinders non-small cell lung cancer (NSCLC) growth and invasion by impacting the insulin-like growth factor (IGF) axis. This study reveals potential new anticancer mechanisms for celecoxib in NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Celecoxib is recognized for its role in tumor prevention and treatment.
- The precise molecular mechanisms underlying celecoxib's anticancer effects remain incompletely understood.
- The insulin-like growth factor (IGF) axis is implicated in various cancers, including non-small cell lung cancer (NSCLC).
Purpose of the Study:
- To investigate the impact of celecoxib on insulin-like growth factor 1 (IGF-1)-induced proliferation and invasion in NSCLC cells.
- To elucidate the molecular pathways through which celecoxib exerts its effects on NSCLC.
- To explore the modulation of the IGF axis as a potential mechanism for celecoxib's anticancer activity.
Main Methods:
- A549 NSCLC cells were treated with IGF-1 in the presence or absence of varying concentrations of celecoxib.
- Cell proliferation and invasion assays were performed to assess cellular responses.
- Western blot analysis was used to examine the expression of phosphorylated type-1 IGF receptor (IGF-1R) and phosphorylated AKT (p-AKT).
- Enzyme-linked immunosorbent assay (ELISA) was employed to measure IGF-binding protein-3 (IGFBP-3) levels.
Main Results:
- Celecoxib demonstrated a dose-dependent inhibition of IGF-1-stimulated cell growth and invasion in A549 cells.
- Celecoxib treatment led to a reduction in the expression of IGF-1R and IGFBP-3.
- The phosphorylation of AKT (p-AKT) was decreased following celecoxib administration.
- These findings indicate that celecoxib interferes with key components of the IGF signaling pathway.
Conclusions:
- Modulating the IGF axis represents a potential novel mechanism for the anticancer effects of celecoxib in NSCLC.
- Celecoxib's ability to inhibit IGF-1-induced growth and invasion highlights its therapeutic potential in NSCLC.
- Further research into the IGF axis may uncover new therapeutic strategies involving celecoxib for NSCLC treatment.
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