Hepatocellular carcinoma (HCC) is one of the most common cancers worldwideand haslimited treatment options. In view of this, zafirlukast (ZAF) was administered orally to DEN-induced HCC rats to evaluate its antineoplastic properties. ELISA, qRT-PCR and Western blot were used to determine the molecular mechanism associated with ZAF therapy for HCC. We found that HCC developed as a result of lower expression of caspases 3 and 9, but their levels returned to normal when the expression of eNOS, BAX, BAD, and Cyt C was decreased and when the expression of iNOS, Bcl-xl, and Bcl-2 was increased. Again, ZAF (80 mg/kg dose) treatment normalized the expression of caspase-mediated apoptotic factors, i.e. BAX and Bcl-2 proteins, as established through Western blot analysis. Later, 1H NMR-based serum metabolomics study revealed that levels of perturbed metabolites in DEN-induced rat serum returned to normal after ZAF administration. Altogether, the antineoplastic potential of ZAF was found to be comparable, and to some degree better, than the marketed chemotherapeutic 5-flurouracil, which may be beneficial for anti-HCC treatment from a future drug design perspective.

中文翻译：

---

扎鲁司特通过激活线粒体介导的细胞凋亡对肝细胞癌的抗肿瘤特性。

肝细胞癌（HCC）是全球最常见的癌症之一，治疗选择有限。有鉴于此，对DEN诱导的HCC大鼠口服给予扎鲁司特（ZAF）以评估其抗肿瘤特性。ELISA，qRT-PCR和Western blot用于确定与ZAF治疗肝癌相关的分子机制。我们发现HCC是由于胱天蛋白酶3和9的较低表达而形成的，但是当eNOS，BAX，BAD和Cyt C的表达降低以及iNOS，Bcl-xl和iNOS的表达降低时，它们的水平恢复正常。 Bcl-2增加。再次，ZAF（80 mg / kg剂量）治疗使caspase介导的凋亡因子，即BAX和Bcl-2蛋白的表达正常化，这是通过Western blot分析确定的。之后，基于1 H NMR的血清代谢组学研究表明，DEN诱导的大鼠血清中摄动的代谢物水平在ZAF给药后恢复正常。总的来说，发现ZAF的抗肿瘤潜力与市售的化学治疗性5-氟尿嘧啶具有可比性，并且在某种程度上更好，从将来的药物设计角度来看，这对于抗HCC治疗可能是有益的。