C1632 suppresses the migration and proliferation of non-small-cell lung cancer cells involving LIN28 and FGFR1 pathway.

Abstract

Chemoresistance and migration represent major obstacles in the therapy of non-small-cell lung cancer (NSCLC), which accounts for approximately 85% of lung cancer patients in clinic. In the present study, we report that the compound C1632 is preferentially distributed in the lung after oral administration in vivo with high bioavailability and limited inhibitory effects on CYP450 isoenzymes. We found that C1632 could simultaneously inhibit the expression of LIN28 and block FGFR1 signalling transduction in NSCLC A549 and A549R cells, resulting in significant decreases in the phosphorylation of focal adhesion kinase and the expression of matrix metalloproteinase-9. Consequently, C1632 effectively inhibited the migration and invasion of A549 and A549R cells. Meanwhile, C1632 significantly suppressed the cell viability and the colony formation of A549 and A549R cells by inhibiting DNA replication and inducing G0/G1 cell cycle arrest. Interestingly, compared with A549 cells, C1632 possesses the same or even better anti-migration and anti-proliferation effects on A549R cells, regardless of drug resistance. In addition, C1632 also displayed the capacity to inhibit the growth of A549R xenograft tumours in mice. Altogether, these findings reveal the potential of C1632 as a promising anti-NSCLC agent, especially for chemotherapy-resistant NSCLC treatment.

• Authors: Jing-Yi Chen, Yu-Jing Chen, Lu Liu, Xiang-Xiang Jin, Zhe Shen, Wen-Bin Chen, Teng Yang, Si-Bei Xu, Guang-Bao Wang, Yi-Nuo Cheng, De-Zhi Cheng, Zhi-Guo Liu, Xiao-Hui Zheng
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 26 Issue 2 Pg. 422-435 (01 2022) ISSN: 1582-4934 [Electronic] England
• PMID: 34913237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Lin28A protein, human
• RNA-Binding Proteins
• FGFR1 protein, human
• Receptor, Fibroblast Growth Factor, Type 1

Topics

• A549 Cells
• Animals
• Apoptosis
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, pathology)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Humans
• Lung Neoplasms (drug therapy, genetics, pathology)
• Mice
• RNA-Binding Proteins (metabolism)
• Receptor, Fibroblast Growth Factor, Type 1 (metabolism)
• Signal Transduction