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Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis while Increases Overall Survival of Mice-bearing Lung Cancers
Zhi-Hua Zhang1,2, Xin-Yan Liu3, Jun-Peng Feng4
1Department of Scientific Research, Hebei Chest Hospital, Shijiazhuang, 050041, China.
Aim:
Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model.
Methods:
The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice.
Results:
Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/β-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor.
Conclusion:
Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/β- catenin pathway.
Insights
A novel fascin inhibitor, NP-G2-044, effectively reduced non-small cell lung cancer (NSCLC) growth and metastasis in preclinical models. This agent shows promise in combination therapies, enhancing existing treatments for lung cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Fascin is an actin-binding protein implicated in promoting tumor metastasis.
- The precise role of fascin in non-small cell lung cancer (NSCLC) progression requires further elucidation.
Purpose of the Study:
- To investigate the anti-cancer effects of NP-G2-044, a novel fascin inhibitor, on human NSCLC cell lines.
- To evaluate the therapeutic potential of NP-G2-044 in a Lewis lung cancer (LCC) mouse model, both as a monotherapy and in combination with other agents.
Main Methods:
- Cell proliferation was assessed using CCK-8 assays.
- Flow cytometry was employed for cell cycle and apoptosis analysis, and to evaluate cell migration and invasion.
- The synergistic effects of NP-G2-044 with cisplatin and PD-1 inhibitors were tested in a murine LCC xenograft model.
Main Results:
- NP-G2-044 significantly inhibited NSCLC cell growth, migration, and invasion in vitro.
- Inhibition of fascin by NP-G2-044 led to reduced epithelial-mesenchymal transition (EMT) markers and was associated with the Wnt/β-catenin pathway.
- In vivo, NP-G2-044 demonstrated tumor growth retardation and improved survival, with synergistic effects observed when combined with cisplatin or a PD-1 inhibitor.
Conclusions:
- Fascin inhibition is a viable strategy to impede NSCLC metastasis.
- NP-G2-044 holds potential for enhancing the efficacy of cisplatin and PD-1 inhibitors through modulation of the Wnt/β-catenin pathway.
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