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Contrary influence of clinically applied sorafenib concentrations among hepatocellular carcinoma patients

Zu-Yau Lin1, Wan-Long Chuang1

  • 1Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|December 10, 2016
PubMed

Insights

Sorafenib

Area of Science:

  • Hepatocellular carcinoma research
  • Molecular oncology
  • Cancer cell biology

Background:

  • Sorafenib's modest efficacy in hepatocellular carcinoma (HCC) may stem from varied cancer cell characteristics or inadequate drug concentrations.
  • Understanding gene expression and cellular response is crucial for optimizing HCC treatment.

Purpose of the Study:

  • To investigate the anti-proliferative effects of sorafenib on primary HCC cells.
  • To analyze differential gene expression of key targets (KDR, PDGFRB, RAF cascade genes) in response to sorafenib.
  • To determine the impact of varying sorafenib concentrations on HCC cell proliferation and gene regulation.

Main Methods:

  • Primary HCC cells from 8 patients were cultured.
  • Cells were treated with clinically relevant sorafenib concentrations (5 and 10 μg/mL).
  • Anti-proliferative effects and differential gene expression (KDR, PDGFRB, RAF cascade) were assessed.

Main Results:

  • Sorafenib exhibited anti-proliferative effects in only one patient, linked to KDR, PDGFRB, and RAF cascade gene down-regulation.
  • Sorafenib promoted proliferation in four patients, often with up-regulation of RAF cascade, PDGFRB, and/or KDR.
  • Increased sorafenib concentration paradoxically up-regulated key genes in several patients, suggesting complex regulatory mechanisms.

Conclusions:

  • Sorafenib's effect on HCC proliferation is complex and not solely mediated by the RAF cascade.
  • Patient-specific responses to sorafenib, including gene expression changes, are diverse and can be contrary.
  • Higher sorafenib concentrations may paradoxically promote angiogenesis and proliferation in some HCC cases.
Keywords:
AngiogenesisHepatocellular carcinomaKDRPDGFRBProliferationSorafenib

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