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

Our study demonstrates that OA effectively inhibits fabp3-mediated drug resistance of HCC cells to sorafenib.

The upregulation of fabp3 in the sorafenib-resistant subset is strongly associated with the ability of HCC cells to evade the lethal effects of sorafenib (Graphical Abstract).

Therefore, evaluating fabp3 levels can be useful in predicting sorafenib tolerance, and the use of OA holds promise for developing personalised treatment strategies for HCC patients.

Our study has limitations, primarily focusing on HCC cell lines rather than real clinical tumours, as sorafenib is mainly used for late-stage HCC patients with limited surgical options.

The study was recently published in the Journal of Clinical and Translational Hepatology.

Source: Xia & He Publishing Inc.