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Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide.When diagnosis is achieved at an early stage, effective therapies that improve long term survival can be applied.Vitamin D ( Vit D)potentiates the anti-tumour effects of many chemotherapeutic. This study investigates the role of Vitamin D on thioacetamide induced HCC in rats. In addition, the effect of Vit D on anti-tumor activity of 5-Fluorouracil(5-FU) was investigated.The rats dividedin to five groups: control, HCC, 5-FU, Vit D and (5-FU+ Vit D) combination groups. HCC was detected by histopathological changes in liver sections and the elevation of serum alpha-fetoprotein (AFP). Treatment with 5-FU+Vit D significantly decreased gene expression of nuclear factor erythroid 2-related factor 2 (NrF2) and transforming growth factor-β1(TGF-β1) at both the gene and protein level and serum AFP concentrations in comparison with their corresponding monotherapy. Moreover, 5-FU+Vit D treatment enhanced apoptosis by increasing caspase-3 gene and protein expression. Vit Denhances antitumor activity of 5-FU in an HCC-induced model and improves liver function of treated animals. Combinationtherapy in a TAA-induced HCC rat model was more effective than 5-FU or Vit D through the modulation of TGF-β1, caspase-3, andNrF2 expressions. |