Oleanolic Acid Restores Drug Sensitivity in Sorafenib-resistant Hepatocellular Carcinoma: Evidence from In Vitro and In Vivo Studies.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic strategies to overcome this resistance. This study aimed to investigate the potential of oleanolic acid (OA), a natural hepatoprotective compound, in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms. METHODS: Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype. The effects of OA on these cells were evaluated by assessing cell invasion, migration, and sensitivity to sorafenib. Gene expression analysis was conducted to identify molecular changes induced by OA treatment, with a focus on fabp3 expression. RESULTS: Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells (p < 0.01). Furthermore, OA treatment downregulated fabp3 expression and restored the cells' sensitivity to sorafenib. CONCLUSIONS: Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC. By reducing cell aggressiveness and restoring drug sensitivity, OA may enhance the therapeutic efficacy of current treatments for advanced HCC.