李勇, 徐林林, 黄璇, 黄登亮, 徐文君, 吕农华, 罗时文. Hedgehog信号通路在食管癌中的异常活化[J]. 中国肿瘤临床, 2012, 39(22): 1761-1764, 1768. DOI: 10.3969/j.issn.1000-8179.2012.22.018
引用本文: 李勇, 徐林林, 黄璇, 黄登亮, 徐文君, 吕农华, 罗时文. Hedgehog信号通路在食管癌中的异常活化[J]. 中国肿瘤临床, 2012, 39(22): 1761-1764, 1768. DOI: 10.3969/j.issn.1000-8179.2012.22.018
shu
Yong LI, Linlin XU, Xuan HUANG, Dengliang HUANG, Wenjun XU, Nonghua LV2, Shiwen LUO. Abnormal Activation of the Hedgehog Signaling Pathway in Esophageal Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(22): 1761-1764, 1768. DOI: 10.3969/j.issn.1000-8179.2012.22.018
Citation: Yong LI, Linlin XU, Xuan HUANG, Dengliang HUANG, Wenjun XU, Nonghua LV2, Shiwen LUO. Abnormal Activation of the Hedgehog Signaling Pathway in Esophageal Cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2012, 39(22): 1761-1764, 1768. DOI: 10.3969/j.issn.1000-8179.2012.22.018
shu

Hedgehog信号通路在食管癌中的异常活化

Abnormal Activation of the Hedgehog Signaling Pathway in Esophageal Cancer

    摘要
  • 摘要:
      目的   探讨Hedgehog（Hh）信号通路与食管鳞状细胞癌（ESCC）的关系。
      方法   采用免疫组织化学随机分析30例ESCC及癌旁组织样本的Hh信号通路中主要组分Smo和Gli2及靶蛋白CyclinD1表达。构建分泌型配体ShhN的条件培养液，利用条件培养液及Hh信号通路激动剂Purmorphamine或Hh通路抑制剂环杷明及GANT61处理CaEs-17细胞后，MTT法检测细胞生存率的变化。
      结果   ESCC组织中的Smo、Gli2和CyclinD1表达普遍高于癌旁组织。含有ShhN的条件培养液能有效激活Hh信号通路下游靶基因CCND1的表达并明显促进食管癌CaEs-17细胞的生存率，提示食管癌中Hh信号通路以配体依赖的方式激活。直接作用于Smo的Hh信号通路激动剂Purmorphamine促进食管癌CaEs-17细胞的生长；而Smo特异性抑制剂环杷明有效地抑制CaEs-17细胞生存率。Gli1/Gli2的抑制剂GANT61比环杷明更为有效地抑制CaEs-17细胞生存率。
      结论   Hh信号通路在ESCC中异常活化，将可能成为新的治疗食管癌的药物靶点。

     

    Abstract:
      Objective   This study explored the relationship between the Hedgehog (Hh) signal pathway and esophageal squamous cell carcinoma (ESCC).
      Methods   The expression levels of the Hh signaling components Smo and Gli2, as well as that of the target protein Cyclin D1, were detected in 30 randomly obtained ESCC specimens (tumor or paraneoplastic tissues) using immunohistochemistry (IHC). The ShhN ligand secretions in the conditional medium were obtained, and the CaEs-17 esophageal cancer cells were treated with the conditional medium, the Hh signaling agonist purmorphamine, the Hh pathway inhibitor cyclopamine, and the Gli1/Gli2 inhibitor GANT61. The cell survival rates were then detected using the methyl thiazolyl tetrazolium (MTT) assay.
      Results   IHC showed that the Smo, Gli2, and Cyclin D1 proteins were highly expressed in the tumor tissues as compared with the pericarcinomatous tissues. The ShhN-containing conditional medium induced the expression of the Hh signaling target gene CCND1 and effectively promoted cell growth. The results indicated that activation of the Hh pathway in esophageal cancer cells was Hh ligand-dependent. Purmorphamine could activate the Hh pathway by directly targeting Smo and consequently promote the survival of CaEs-17 cells, whereas the Smo-specific inhibitor cyclopamine could decrease the cell survival rate. GANT61 appeared to be a more powerful inhibitor of CaEs-17 survival as compared with cyclopamine.
      Conclusions   The Hh signaling pathway is abnormally activated in ESCC, which may be a useful approach for treating esophageal cancer.

     

    • HTML全文
    • 参考文献(10)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回