Patil Mohini A, Zhang Ji, Ho Coral, Cheung Siu-Tim, Fan Sheung-Tat, Chen Xin
Department of Biopharmaceutical Sciences and Liver Center, University of California, San Francisco, California 94143-0446, USA.
Cancer Biol Ther. 2006 Jan;5(1):111-7. doi: 10.4161/cbt.5.1.2379. Epub 2006 Jan 5.
Hepatocellular carcinoma (HCC) is the fourth most common malignancy and one of the leading causes of death world wide. Signaling pathways important for tumor initiation and progression in HCC are poorly understood. Hedgehog signaling (Hh) has been implicated in multiple events during development and has also been proposed to play important roles in several tumor types. However, it remains unclear whether this pathway is activated in HCC. Here, we report the detection of transcripts for hedgehog pathway signaling molecules in both HCC cell lines and tumor samples. Quantitative real-time RT-PCR also revealed the decreased expression of Hip1 and increased expression of Gli1 and smo in HCC samples compared with nontumor liver tissues. Blocking the hedgehog pathway with cyclopamine inhibited proliferation, induced apoptosis and repressed c-Myc and cyclin D expression in a subset of HCC cell lines. The study therefore, for the first time, provides evidence that hedgehog signaling may be activated in some HCC tumors. The results also indicate that the hedgehog pathway may be a new candidate for therapeutic targeting in HCC.
肝细胞癌（HCC）是第四大常见恶性肿瘤，也是全球主要的死亡原因之一。目前对HCC中肿瘤起始和进展所重要的信号通路了解甚少。刺猬信号通路（Hh）在发育过程中的多个事件中发挥作用，也被认为在几种肿瘤类型中起重要作用。然而，该通路在HCC中是否被激活仍不清楚。在此，我们报告了在HCC细胞系和肿瘤样本中检测到刺猬信号通路信号分子的转录本。定量实时RT-PCR还显示，与非肿瘤肝组织相比，HCC样本中Hip1表达降低，Gli1和smo表达增加。用环杷明阻断刺猬信号通路可抑制一部分HCC细胞系的增殖、诱导凋亡并抑制c-Myc和细胞周期蛋白D的表达。因此，该研究首次提供了证据表明刺猬信号可能在某些HCC肿瘤中被激活。结果还表明，刺猬信号通路可能是HCC治疗靶点的新候选者。
