Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model

In Vivo. 2024 May-Jun;38(3):1079-1093. doi: 10.21873/invivo.13542.

Abstract

Background/aim: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment.

Materials and methods: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms.

Results: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling.

Conclusion: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

Keywords: EGFR; Quetiapine; hepatocellular carcinoma; radiosensitizer; radiotherapy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / radiotherapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / radiotherapy
  • Male
  • Mice
  • Quetiapine Fumarate* / pharmacology
  • Quetiapine Fumarate* / therapeutic use
  • Xenograft Model Antitumor Assays*

Substances

  • Quetiapine Fumarate