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Published on: August 11, 2017
A monoclonal antibody against basic fibroblast growth factor attenuates cisplatin resistance in lung cancer by
Penghui Hu1,2, Kaman So1, Hongjie Chen3
1Department of Oncology, 162698The First Affiliated Hospital of Jinan University, Guangzhou, China.
Abstract:
: To investigate the underlying mechanisms of how the basic fibroblast growth factor monoclonal antibody (bFGFmAb) attenuates cisplatin (DDP) resistance in lung cancer using A549 cells and cisplatin-resistant A549 cells (A549/DDP). : Cancer cell proliferation, cell viability, and 50% inhibitory concentration (IC50) of cisplatin were assessed. Transwell assays were utilized to evaluate the invasion activity of tumor cells in response to treatment. Epithelial-to-mesenchymal transition markers and drug resistance proteins were analysed using Western blots. We demonstrate that the bFGFmAb inhibits the proliferation and invasion of both A549 and A549/DDP cells. The bFGFmAb increases cisplatin sensitivity of both A549 and A549/DDP cells as evidenced by an increase in the IC50 of cisplatin in A549 and A549/DDP cells. Furthermore, bFGFmAb significantly increases the expression of E-cadherin, whilst decreasing the expression of N-cadherin and bFGF in both cell lines, thereby showing inhibition of epithelial-to-mesenchymal transition. In addition, we demonstrate that bFGFmAb significantly reduces the expression of the lung resistance protein. Our data suggests that the humanized bFGFmAb is a promising agent to attenuate cisplatin resistance in NSCLC. The underlying mechanism for this effect of bFGFmAb may be associated with the inhibition of epithelial-to-mesenchymal transition and reduced expression of lung resistance protein.
Insights
Basic fibroblast growth factor monoclonal antibody (bFGFmAb) combats cisplatin resistance in lung cancer cells. This antibody inhibits cell growth, invasion, and epithelial-to-mesenchymal transition, offering a promising therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cisplatin resistance is a major challenge in non-small cell lung cancer (NSCLC) treatment.
- Basic fibroblast growth factor (bFGF) plays a role in cancer progression and drug resistance.
Purpose of the Study:
- To investigate the efficacy of basic fibroblast growth factor monoclonal antibody (bFGFmAb) in overcoming cisplatin resistance in lung cancer.
- To elucidate the underlying mechanisms by which bFGFmAb attenuates cisplatin resistance.
Main Methods:
- Cell proliferation, viability, and IC50 assays were performed using A549 and A549/DDP cells.
- Transwell assays assessed cell invasion.
- Western blotting analyzed epithelial-to-mesenchymal transition markers and drug resistance proteins.
Main Results:
- bFGFmAb inhibited proliferation and invasion in both A549 and A549/DDP cells.
- bFGFmAb increased cisplatin sensitivity, evidenced by altered IC50 values.
- bFGFmAb suppressed epithelial-to-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin and bFGF expression.
- bFGFmAb reduced lung resistance protein expression.
Conclusions:
- Humanized bFGFmAb shows potential in attenuating cisplatin resistance in NSCLC.
- Mechanisms involve inhibition of epithelial-to-mesenchymal transition and reduced lung resistance protein expression.
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