Hepatocellular carcinoma (HCC) is one of the most aggressive
malignancies, with continuously increasing cases and fatalities. Diagnosis often occurs in the advanced stages, confining patients to systemic
therapies such as
sorafenib.
Sorafenib (SB), a multi-
kinase inhibitor, has not yet demonstrated sufficient efficacy against advanced HCC. There is a strong argument in favor of studying its use in combination with other medications to optimize the therapeutic results. According to our earlier work,
crocin (CR), a key bioactive component of saffron, hinders HCC development and
liver cancer stemness. In this study, we investigated the
therapeutic use of CR or its combination with SB in a cirrhotic rat model of HCC and evaluated how effectively SB and CR inhibited
tumor growth in this model.
Diethylnitrosamine (DEN) was administered intraperitoneally to rats once a week for 15 weeks, leading to
cirrhosis, and then 19 weeks later, leading to multifocal HCC. After 16 weeks of
cancer induction, CR (200 mg/kg daily) and SB (10 mg/kg daily) were given orally to rats for three weeks, either separately or in combination. Consistently, the combination treatment considerably decreased the incidence of dyschromatic nodules, nodule multiplicity, and dysplastic nodules when compared to the HCC group of single
therapies. Combined
therapy also caused the highest degree of apoptosis, along with decreased proliferating and β-
catenin levels in the
tumor tissues. Additionally, when rats received combined
therapy with CR, it showed anti-inflammatory characteristics where
nuclear factor kappa B (NF-κB) and
cyclooxygenase-2 (Cox-2) were considerably and additively lowered. As a result, CR potentiates the suppressive effects of SB on
tumor growth and provides the opportunity to strengthen the
therapeutic effects of SB in the treatment of HCC.