Systemic Drug Effects in Vortioxetine-Induced Time-Series Datasets

Area of Science:

• Oncology
• Systems Biology
• Pharmacology

Background:

• Glioblastoma is a complex cancer with intertwined signaling pathways.
• Understanding drug-induced gene regulatory networks is crucial for cancer therapy.
• Vortioxetine's effects on glioblastoma cellular mechanisms require detailed investigation.

Purpose of the Study:

• To infer gene regulatory networks in vortioxetine-treated glioblastoma cells.
• To investigate vortioxetine's systemic effects on cancer-related pathways.
• To identify key genes and pathways modulated by vortioxetine.

Main Methods:

• Utilized an ordinary differential equation (ODE)-based inverse problem approach.
• Analyzed time-series gene expression datasets generated at multiple time points (0-24 h).
• Focused on the GLIOMA and ERBB signaling pathways.

Main Results:

• Vortioxetine activated PIK3R5 and CALML6 while inhibiting proto-oncogenes JUN, CDK4, and CCND1.
• PIK3R5 activation was consistently linked to PAK6.
• Distinct gene expression changes were observed between 6 and 22 hours post-treatment, with notable genes including CRK, JUN, BRAF, and MAP2K2.

Conclusions:

• Vortioxetine demonstrates a time-dependent inhibitory effect on key proto-oncogenes (JUN, CCND1) in glioblastoma.
• The findings suggest vortioxetine's potential role in modulating cancer progression through gene network regulation.
• Further research into vortioxetine's anti-cancer mechanisms is warranted.