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Assessment of the main signaling pathways involved in the combined therapy of hepatocellular carcinoma using Sorafenib and NK cells in xenograft mice model

  • 0Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Qom University of Medical Sciences, Qom, Iran.
Toxicology Reports +

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October 6, 2025

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October 6, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Combination therapy of Sorafenib and Natural Killer (NK) cells did not improve hepatocellular carcinoma (HCC) treatment. This study found that combining Sorafenib with NK cells decreased their individual anti-cancer effectiveness, suggesting it may not be a successful therapeutic option.

Area Of Science

  • Oncology
  • Immunology
  • Pharmacology

Background

  • Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally.
  • Sorafenib is the sole FDA-approved drug for HCC, offering limited survival benefits and significant toxicities.
  • Natural Killer (NK) cells show promise in HCC treatment, leading to investigations into combination therapy.

Purpose Of The Study

  • To investigate the effects of Sorafenib and NK cell therapy, individually and in combination, on HCC progression.
  • To analyze the impact on key signaling pathways involved in HCC development.
  • To evaluate the safety and efficacy of combined Sorafenib and NK cell treatment.

Main Methods

  • A xenograft model of HCC was established using human HepG2 cells in nude mice.
  • Mice were divided into four groups: Control, Sorafenib, NK cells, and Sorafenib plus NK cells.
  • Gene expression analysis (Quantitative real-time PCR) and biochemical assays (liver/kidney enzymes) were performed.

Main Results

  • Sorafenib and NK cell monotherapies reduced proliferative and anti-apoptotic factors.
  • Combined therapy showed no significant difference compared to the control group.
  • NK cell effector function genes were upregulated in the NK cell group but inhibited in the combination group.
  • Safety markers (AST, ALT, BUN, Cr) remained within normal ranges across all groups.

Conclusions

  • The combination of Sorafenib and NK cells at the tested dosage decreased the anti-cancer efficacy of both agents.
  • This combination therapy may not be a successful strategy for treating hepatocellular carcinoma.
  • Further research is needed to explore alternative combination strategies or dosages.

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