Blockade of the sonic hedgehog pathway effectively inhibits the growth of hepatoma in mice: An in vivo study

Jeng,Kuo-Shyang; Sheen,I-Shyan; Jeng,Wen-Juei; Yu,Ming‑Che; Tsai,Hsin-Hua; Chang,Fang-Yu; Su,Jui-Chih

doi:10.3892/ol.2012.935

Blockade of the sonic hedgehog pathway effectively inhibits the growth of hepatoma in mice: An in vivo study

Authors:
- Kuo-Shyang Jeng
- I-Shyan Sheen
- Wen-Juei Jeng
- Ming‑Che Yu
- Hsin-Hua Tsai
- Fang-Yu Chang
- Jui-Chih Su
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Affiliations: Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan, R.O.C., Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taipei, Taiwan, R.O.C., Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan, R.O.C.
Published online on: September 24, 2012 https://doi.org/10.3892/ol.2012.935
Pages: 1158-1162

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Abstract

Hepatocellular carcinoma (HCC), a worldwide malignancy, is prevalent in Asian countries. For individuals with unresectable HCC, the effect of chemotherapy or the present target therapy is limited. There is an urgent need to find innovative new therapies. It is believed that sonic hedgehog (Shh) pathway activation may be essential for hepatocarcinogenesis. In the present study, we conducted an in vivo animal study using an Shh pathway inhibitor to elucidate the effect of treatment upon mice with HCC. Eighty C57BL/6 mice were divided into 4 groups (groups A, B, C and D, with group A serving as a control; n=20 for each). We injected mouse hepatoma Mistheton Lectin-1 cells (5xl06 cells/20 µl) into the left liver of each mouse in groups B, C and D. In the second week, we analyzed each mouse to assess the tumor growth status. Following the tumor injection, group B did not receive any additional intraperitoneal (i.p.) injection, group C received cyclopamine 10 mg/kg/day i.p. and group D received cyclopamine 30 mg/kg/day i.p. every day for 10 days. After an interval of 4 weeks, harvesting and analysis of the liver was performed for each mouse. Tumor size measurement and real‑time PCR of Shh pathway factors (Shh, Ptch-1, Gli-1 and Smoh) for livers of group A and tumors of group B, C and D were undertaken. The decrease in the tumor size of group D was found to be statistically significant (P=0.047) when compared with groups B or C. The decrease of Shh mRNA of both groups C and D had borderline significance when compared with group B. However, Gli-1 mRNA of group D has statistically significant difference (P=0.044) when compared with group A, B or C. Inhibition of the Shh pathway significantly decreases the size and Gli-1 mRNA expression of the tumor. The Shh pathway may be an effective treatment target for HCC in the future.

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