Cationic liposomes induce cytotoxicity in HepG2 via regulation of lipid metabolism based on whole-transcriptome...

Area of Science:

• Molecular Biology
• Systems Biology
• Toxicology

Background:

• Cationic liposomes (CLs) are utilized as non-viral vectors for gene transfer and drug delivery.
• The precise molecular mechanisms underlying CL-induced cytotoxicity remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular mechanisms of cationic liposome (CL) cytotoxicity using a systems biology approach.
• To identify key genes and pathways affected by CL exposure in HepG2 cells.

Main Methods:

• Whole-transcriptome sequencing was employed to analyze gene expression changes in HepG2 cells treated with CLs.
• Computational methods, including gene ontology and pathway analysis, were used to identify affected biological processes.
• Quantitative real-time PCR (qRT-PCR) was performed to validate the expression levels of selected genes.

Main Results:

• Cationic liposomes demonstrated a concentration-dependent cytotoxicity with an IC50 of 120 μg/ml in HepG2 cells after 24 hours.
• Whole-transcriptome sequencing identified 220 differentially expressed genes (DEGs), predominantly involved in cholesterol, steroid, and lipid biosynthesis and metabolism.
• No significant cell cycle arrest was observed via flow cytometry analysis.

Conclusions:

• The study provides a comprehensive understanding of the molecular mechanisms underlying CL cytotoxicity.
• The findings highlight the significant impact of CLs on lipid metabolism pathways in HepG2 cells.