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Erschienen in: Journal of Cancer Research and Clinical Oncology 5/2009

01.05.2009 | Original Paper

Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma

verfasst von: Zheng Wang, Jian Zhou, Jia Fan, Chang-Jun Tan, Shuang-Jian Qiu, Yao Yu, Xiao-Wu Huang, Zhao-You Tang

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 5/2009

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Abstract

Purpose

Immunosuppressive therapy after liver transplantation for hepatocellular carcinoma (HCC) is one of the major contributory factors for HCC recurrence and metastasis. Sirolimus, a potent immunosuppressant, has been reported to be an effective inhibitor in a variety of tumors. The present study is designed to explore whether sirolimus could block the growth and metastatic progression of HCC.

Methods

MHCC97H cells were used as targets to explore the effect of sirolimus on cell cycle progression, apoptosis, proliferation, and its antiangiogenic mechanism. LCI-D20, a highly metastatic model of human HCC in nude mice, was also used as the model tumor to explore the effect of sirolimus on tumor growth and metastatic progression.

Results

In vitro, sirolimus induced cell cycle arrest at the G1 checkpoint and blocked proliferation of MHCC97H cells but did not induce apoptosis. In vivo, sirolimus prevented tumor growth and metastatic progression in LCI-D20. Intratumoral microvessel density and circulating levels of VEGF in tumor-bearing mice were also significantly reduced in sirolimus treatment group. Quantitative RT-PCR showed that sirolimus down-regulated the mRNA expression of VEGF and HIF-1a, but not of bFGF, and TGF-b in MHCC97H cells. Furthermore, western blot analysis confirmed that sirolimus also decreased expression of HIF-1a at protein level, in parallel with the down-regulation of the levels of VEGF protein excretion in a time-dependent manner as compared to untreated control cells following anoxia.

Conclusions

The immunosuppressive macrolide sirolimus prevents the growth and metastatic progression of HCC, and suppresses VEGF synthesis and secretion by downregulating HIF-1a expression. Sirolimus may be useful for clinical application in patients who received a liver transplant for HCC.
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Metadaten
Titel
Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma
verfasst von
Zheng Wang
Jian Zhou
Jia Fan
Chang-Jun Tan
Shuang-Jian Qiu
Yao Yu
Xiao-Wu Huang
Zhao-You Tang
Publikationsdatum
01.05.2009
Verlag
Springer-Verlag
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 5/2009
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-008-0506-z

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