期刊
ONCOLOGY LETTERS
卷 4, 期 6, 页码 1158-1162出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2012.935
关键词
hepatocellular carcinoma; sonic hedgehog pathway
类别
资金
- Far Eastern Memorial Hospital
- National Science Council, Executive Yuan, Taiwan [NSC-97-2314-B-195-008-MY3]
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 (5x10(6) cells/20 mu l) 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-I, Gli-I 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-I m RNA 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-I mRNA expression of the tumor. The Shh pathway may be an effective treatment target for HCC in the future.
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