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Updated: Jun 22, 2026
Generation of Subcutaneous and Intrahepatic Human Hepatocellular Carcinoma Xenografts in Immunodeficient Mice
Published on: September 25, 2013
[Effects of sirolimus on the growth of transplanted hepatocellular carcinoma]
Jian Zhang1, Hua Li, Gen-shu Wang
1Liver Transplantation Center, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. zhangjian629@sina.com
Objective:
To study the effects of sirolimus (SRL) on the growth of transplanted human hepatocellular carcinoma (HCC) in nude mice.
Methods:
HepG2 cells were Implanted into the liver of nude mice. The implanted mice were then treated with SRL and tacrolimus (FK506). The expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected by immunohistology, microvessel density (MVD) was counted by immunostaining with anti-CD34 antibody for endothelial cells. Tumor apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay.
Results:
The tumor weight was (352+/-38) mg, (683+/-53) mg and (675+/-45) mg in SRL, FK506 and control group respectively. The tumor weight was significantly decreased in SRL group (P < 0.01), and there was no difference between FK506 group and control group. The expression of VEGF and PCNA protein was remarkably down-regulated in SRL group compared to control group (P < 0.05), and it was not significantly different between FK506 group and control group (P > 0.05). Compared to the control group, MVD was significanly decreased in SRL group, and the apoptosis index of tumor cell was significantly higher in SRL group (P < 0.01).
Conclusion:
SRL inhibits transplanted HCC tumor growth by reducing tumor angiogenesis, inhibiting tumor proliferation and inducing tumor apoptosis.
Insights
Sirolimus (SRL) effectively inhibited transplanted hepatocellular carcinoma (HCC) growth in mice. SRL reduced tumor angiogenesis, proliferation, and increased apoptosis, offering a potential therapeutic strategy for HCC.
Area of Science:
- Oncology
- Pharmacology
Context:
- Hepatocellular carcinoma (HCC) is a prevalent cancer with limited treatment options.
- Investigating novel therapeutic agents for HCC is crucial.
Purpose:
- To evaluate the efficacy of sirolimus (SRL) in inhibiting the growth of transplanted human HCC in nude mice.
- To assess SRL's impact on tumor angiogenesis, proliferation, and apoptosis.
Summary:
- Sirolimus (SRL) treatment significantly reduced tumor weight in mice with transplanted HCC compared to controls.
- SRL downregulated the expression of vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA).
- SRL decreased microvessel density (MVD) and increased tumor cell apoptosis.
Impact:
- Sirolimus demonstrates significant anti-tumor effects against HCC in vivo.
- SRL's mechanism involves inhibiting angiogenesis and proliferation while promoting apoptosis.
- These findings suggest SRL as a potential therapeutic agent for HCC treatment.
