Expression of Sonic Hedgehog Signaling Components in Hepatocellular Carcinoma and Cyclopamine-induced Apoptosis Through Bcl-2 Downregulation In Vitro

Chen, Xi-lin; Cheng, Qing; She, Miaorong; Wang, Qian; Huang, Xiaohui; Cao, Liangqi; Fu, Xiaohong; Chen, Jingsong

doi:10.1016/j.arcmed.2010.06.003

Cited by 45 publications

(49 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…tGli-1 has a greater tendency than Gli-1 to promote glioblastoma and breast cancer cell migration and invasion by enhancing the expression of MMP-2 and MMP-9. 20 Enhanced Hh signaling has been identified in~70% of human HCC specimens; 30 however, no previous study has Figure 5. Relative gene expression levels of Gli-1, Gli-2, twist-1 and snail-1 in Huh-7 subpopulations and effects on LDE225.…”

Section: Discussionmentioning

confidence: 99%

Aberrant hedgehog signaling is responsible for the highly invasive behavior of a subpopulation of hepatoma cells

et al. 2015

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Aberrant hedgehog signaling is responsible for the highly invasive behavior of a subpopulation of hepatoma cells

et al. 2015

View full text Add to dashboard Cite

“…10 Hedgehog signaling is quiescent in adult tissues. Overexpression of Hh pathway molecules, such as sonic Hh, PTCH1, SMO, and Gli-1/2, has been reported in 60-70% of HCC specimens, 11,12 and dysregulated expression of Hh molecules is one of disordered signaling mechanisms crucial for hepatic carcinogenesis 13 and highly metastatic behavior of HCC. 14 Hh signaling inhibitors, such as vismodegib (GDC--0449) and sonidegib (LDE225), are approved for the treatment of advanced basal cell carcinoma; 15 and sonidegib is in phase I-II clinical trials for the treatment of a variety of malignancies, including esophageal, pancreatic, ovarian cancers, and hepatocellular carcinoma.…”

mentioning

confidence: 99%

Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter

Ding

Xiao

Zou

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…Cyclopamine, a well-known antagonist of Smoothened (Smoh), may inhibit the Shh pathway. The effect of cyclopamine on hepatocarcinogenesis has been described in a previous study (19). However, the in vivo effect remains unknown.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2012

View full text Add to dashboard Cite

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 (5xl0 6 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.

show abstract

Expression of Sonic Hedgehog Signaling Components in Hepatocellular Carcinoma and Cyclopamine-induced Apoptosis Through Bcl-2 Downregulation In Vitro

Cited by 45 publications

References 41 publications

Aberrant hedgehog signaling is responsible for the highly invasive behavior of a subpopulation of hepatoma cells

Aberrant hedgehog signaling is responsible for the highly invasive behavior of a subpopulation of hepatoma cells

Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter

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

Contact Info

Product

Resources

About