Tumor Biology

, Volume 37, Issue 2, pp 1617–1625 | Cite as

Comparative study of the effects of PEGylated interferon-α2a versus 5-fluorouracil on cancer stem cells in a rat model of hepatocellular carcinoma

  • Tarek Kamal Motawi
  • Noha Ahmed El-Boghdady
  • Abeer Mostafa El-Sayed
  • Hebatullah Samy Helmy
Original Article

Abstract

Cancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor-initiating, metastatic, and drug resistance properties. This study was conducted to evaluate the effects of PEGylated interferon-α2a (PEG-IFN-α2a) and 5-fluorouracil (5-FU) on the expression of CSC markers and on specific pathways that contribute to the propagation of CSCs in HCC. HCC was initiated in rats using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for 6 weeks. After the appearance of dysplastic nodules, the animals received PEG-IFN-α2a or 5-FU for 8 weeks. CSC markers (OV6, CD90) and molecules related to transforming growth factor β (TGF-β) and other signaling pathways were assessed in hepatic tissues. The PEG-IFN-α2a treatment effectively suppressed the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic expression of TGF-β receptor II (TGF-βRII) and β2-spectrin (β2SP), and significantly reduced the elevated hepatic expression of TGF-β1, interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3), and vascular endothelial growth factor (VEGF). In contrast, the 5-FU treatment failed to reduce the overexpression of CSC markers and barely affected the disrupted TGF-β signaling. Furthermore, it had no effect on angiogenesis or nitrosative stress. PEG-IFN-α2a, but not 5-FU, could reduce the propagation of CSCs during the progression of HCC by upregulating the disrupted TGF-β signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis.

Keywords

Hepatocellular carcinoma PEGylated interferon-α2a 5-Fluorouracil Cancer stem cells 

Notes

Acknowledgments

The present study was completely funded by Cairo University.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Biochemistry, Faculty of PharmacyCairo UniversityCairoEgypt
  2. 2.Department of Pathology, National Cancer InstituteCairo UniversityCairoEgypt

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