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.
肝细胞癌（HCC）是一种极具侵袭性的恶性肿瘤，其发病率和死亡率持续上升。该病常在晚期才被诊断，使患者只能接受索拉非尼等全身性治疗。索拉非尼（SB）作为一种多激酶抑制剂，在治疗晚期HCC方面尚未显示出足够疗效。因此，有必要研究其与其他药物联合使用以优化治疗效果。根据我们前期的研究，藏红花的主要生物活性成分西红花苷（CR）能够抑制HCC的发展及肝癌干细胞特性。本研究探讨了CR单独使用或与SB联合应用在肝硬化大鼠HCC模型中的治疗效果，并评估了SB和CR在该模型中抑制肿瘤生长的有效性。通过每周腹腔注射二乙基亚硝胺（DEN）持续15周诱导大鼠肝硬化，随后在第19周形成多灶性HCC。在诱导肝癌16周后，分别单独或联合给予大鼠CR（每日200 mg/kg）和SB（每日10 mg/kg）口服治疗三周。与单药治疗的HCC组相比，联合治疗显著降低了异色结节发生率、结节多重性和异型增生结节数量。联合治疗还诱导了最高程度的细胞凋亡，同时降低了肿瘤组织中增殖细胞和β-连环蛋白的水平。此外，当大鼠接受CR联合治疗时，表现出抗炎特性，其中核因子κB（NF-κB）和环氧合酶-2（Cox-2）水平显著且叠加性降低。因此，CR能增强SB对肿瘤生长的抑制作用，并为强化SB治疗HCC的疗效提供了可能。
肿瘤(癌症)患者之家