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Updated: Jan 21, 2026
A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
Published on: October 24, 2015
Thymoquinone upregulates TRAIL/TRAILR2 expression and attenuates hepatocellular carcinoma in vivo model
Sahar A Helmy1, Mohamed El-Mesery1, Amro El-Karef2
1Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Aims:
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. Indeed, chemotherapeutic drugs-induced systemic toxicity results in suboptimal cancer treatment. Consequently, there is a need for exploring of a safe and effective therapy for cancer patients. This study aimed to evaluate the hepatoprotective effect of thymoquinone (TQ) against thioacetamide (TAA)-induced HCC. Also, we investigated TQ's ability to sensitize cancer cells toward TRAIL/TRAILR2 apoptotic pathway.
Main Methods:
Forty male Sprague Dawley rats were divided into 4 groups (n = 10) as follows: control group, CMC group, HCC group and HCC + TQ group. Serum levels of liver function biomarkers and Alpha-Fetoprotein (AFP), as well as hepatic levels of glutathione (GSH) and Alpha-Fetoprotein (MDA) were measured. Transforming growth factor-beta 1 (TGF-β1), TRAILR2, TRAIL, caspase-3, caspase-9, caspase-8 and B cell lymphoma-2 (Bcl-2) mRNA levels were assessed by Quantitative, Real-Time PCR. Fibrosis percentage and necroinflammation were quantified by histopathological examination.
Key Findings:
Our results indicated improvement in liver functions, decrease in AFP level and attenuation of HCC progression in TQ treated rats. TQ upregulated TRAIL/TRAILR2 and subsequently enhanced apoptosis as hinted by caspase-3 upregulation and Bcl-2 downregulation. Also, TQ decreased TGF-β1 gene expression level. Moreover, HCC + TQ group showed significant increase in hepatic GSH level and marked decrease in hepatic MDA level.
Significance:
This study proved that TQ is able to suppress HCC development via decreasing oxidative stress, suppression of TGF-β1 and induction of TRAIL-mediated apoptosis.
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