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Updated: Sep 8, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Osthole Increases the Sensitivity of Liver Cancer to Sorafenib by Inhibiting Cholesterol Metabolism

Ke Fan1, Hui Huang1, Ying Zhao1,2

  • 1Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu Province, China.

Nutrition and Cancer
|June 16, 2022
PubMed

Insights

Osthole enhances sorafenib

Area of Science:

  • Hepatocellular Carcinoma Research
  • Natural Product Pharmacology
  • Cancer Drug Sensitization

Background:

  • Liver cancer poses a significant health challenge.
  • Sorafenib is a standard treatment, but resistance is common.
  • Osthole's role in sensitizing liver cancer to sorafenib is unclear.

Purpose of the Study:

  • To investigate osthole's effect on liver cancer sensitivity to sorafenib.
  • To explore the underlying sensitization mechanisms.

Main Methods:

  • In vitro studies using HCCLM3, HCCLM3-SR, and SK-Hep-1 cells.
  • In vivo xenograft mouse models treated with osthole and sorafenib.
  • Analysis of proliferation, colony formation, migration, tumor growth, and cholesterol metabolism markers.

Main Results:

  • Osthole and sorafenib combination showed synergistic inhibition of cancer cell proliferation, colony formation, and migration.
  • Combined treatment significantly reduced tumor volume and weight in vivo.
  • Osthole decreased cholesterol and LDL-cholesterol levels and downregulated SREBP-2c, HMGCR, and LDLR protein expression.

Conclusions:

  • Osthole enhances liver cancer sensitivity to sorafenib.
  • The mechanism involves downregulating SREBP-2c, HMGCR, and LDLR, inhibiting cholesterol metabolism.

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