Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis
Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis
复制标题
Hedgehog信号通路调控人胰腺癌细胞增殖和转移
DOI：
10.3892/or.2012.2210
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发表时间：
2013-03-01
期刊：
影响因子：
4.2
通讯作者：
Yang, Yin-Mo
中科院分区：
文献类型：
--
作者：
Hao, Kun;Tian, Xiao-Dong;Yang, Yin-Mo
胰腺癌是最具侵袭性和破坏性的恶性肿瘤之一。Hedgehog（Hh）通路在胰腺癌的发生和发展中起重要作用。本研究的目的是检测Hh通路在人胰腺癌组织样品和胰腺癌细胞系中的激活，以及Hh通路介导的对胰腺癌细胞增殖和侵袭作用的分子机制。采用RT-PCR方法检测胰腺癌组织和胰腺癌细胞系中Hh分子的表达水平。采用流式细胞术、MTT、集落形成试验和Transwell侵袭试验评价Hh通路在细胞增殖和侵袭中的作用，采用流式细胞术和RT-PCR评价肿瘤干细胞标志物和上皮-间质转化（EMT）的表达。致瘤性测定用于进一步研究Hh途径在体内的作用。人胰腺癌组织样本和胰腺癌细胞系中Hh分子高表达。Hh通路的抑制通过抑制PI 3 K/AKT通路和癌症干细胞显著降低细胞增殖并诱导细胞凋亡。此外，Hh信号通路的抑制通过抑制转录因子Snail和Slug的活化而显著抑制EMT，这与显著降低的胰腺癌细胞侵袭相关，表明Hh信号通路参与早期转移。这些结果表明，Hh途径的激活是常见事件。抑制Hh通路可能成为胰腺癌治疗新策略的潜在分子靶点。
Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and Transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.