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Decrease in growth factor receptors after treatment with serine protease inhibitor ONO-3403.

Takaki Hiwasa¹, Hideaki Shimada, Takenori Ochiai

¹Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. hiwasa@med.m.chiba-u.ac.jp

International Journal of Oncology

|March 15, 2002

Summary

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ONO-3403, a serine protease inhibitor derivative, suppresses cancer cell growth by reducing tyrosine phosphorylation of growth factor receptors like PDGF and EGF receptors.

Area of Science:

Molecular Biology
Cell Biology
Biochemistry

Background:

Serine protease inhibitors are investigated for therapeutic potential.
ONO-3403 is a potent derivative of FOY-305 with enhanced protease-inhibitory activity.
Ras-transformed cells exhibit distinct responses to ONO-3403 compared to normal cells.

Purpose of the Study:

To investigate the growth-suppressive mechanisms of ONO-3403 in cancer cells.
To identify the molecular targets affected by ONO-3403 treatment.
To explore the role of growth factor receptor signaling in ONO-3403's effects.

Main Methods:

Cell culture of NIH3T3 and ras-NIH cells.
Flow cytometry to analyze cell cycle distribution.
Western blot analysis using anti-phosphotyrosine antibody.

Related Experiment Videos

Immunoprecipitation with anti-PDGF-receptor antibody.

Main Results:

ONO-3403 treatment led to cell cycle arrest in G1 phase and increased S phase in ras-NIH cells.
A significant decrease in tyrosine phosphorylation of a 180-kDa protein (pY-p180) was observed.
pY-p180 was identified as platelet-derived growth factor (PDGF) receptor in NIH3T3 cells.
In T.Tn human esophageal carcinoma cells, ONO-3403 also reduced pY-p180, identified as epidermal growth factor receptor (EGFR).

Conclusions:

ONO-3403 induces growth suppression in cancer cells.
The mechanism involves the down-regulation of cell surface growth factor receptors, including PDGF and EGFR.
This suggests a potential therapeutic strategy targeting growth factor receptor signaling.