Integrating Network Pharmacology and Experimental Validation of Oleanolic Acid Targeting the PPARα-CPT1A Axis to Modulate Lipid Metabolism in Hepatocellular Carcinoma Cells

Patients with liver cancer frequently exhibit abnormal liver function and disorders in lipid metabolism. This study investigates the effects of Oleanolic acid (OA) on hepatocellular carcinoma (HCC) through the regulation of lipid metabolism. Computational simulations identified six core targets of OA, including PPARα, HMGCR, and ESR1, with stable binding confirmed through molecular docking and dynamics analyses. The experiments demonstrated that OA reduced intracellular lipid accumulation, suppressed cell migration (p < 0.05), and promoted apoptosis. The levels of lipid droplets and triglycerides (TG) were significantly decreased (p < 0.05). The expression levels of lipid metabolism-related genes, including PPARA, CPT1A, FASN, and HMGCR, were assessed using qRT-PCR (p < 0.05). Additionally, protein expression levels were analyzed through Western blotting (p < 0.05). Furthermore, the combination of OA with the antagonist GW6471 enhanced tumor suppression, while the combination with the agonist Pemafibrate reversed the effects of OA. Compared to OA alone, the antagonist combination significantly reduced PPARα and CPT1A protein expression (p < 0.05), whereas Pemafibrate upregulated these proteins (p < 0.05). In conclusion, OA exerts its anti-lipid metabolism effects in HCC by modulating the PPARα-CPT1A axis, indicating its potential therapeutic value in liver cancer treatment.