CAJ | 학술논문

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.
목적:탐토Hedgehog(Hh)신호통로여식관린상세포암(ESCC)적관계.방법:채용면역조직화학수궤분석30례ESCC급암방조직양본적Hh신호통로중주요조분Smo화Gli2급파단백CyclinD1표체.구건분비형배체ShhN적조건배양액,이용조건배양액급Hh신호통로격동제Purmorphamine혹Hh통로억제제배파명급GANT61처리CaEs-17세포후,MTT법검측세포생존솔적변화.결과:ESCC조직중적Smo、Gli2화CyclinD1표체보편고우암방조직.함유ShhN적조건배양액능유효격활Hh신호통로하유파기인CCND1적표체병명현촉진식관암CaEs-17세포적생존솔,제시식관암중Hh신호통로이배체의뢰적방식격활.직접작용우 Smo 적 Hh 신호통로격동제 Purmorphamine 촉진식관암 CaEs-17세포적생장;이 Smo 특이성억제제배파명유효지억제CaEs-17세포생존솔.Gli1/Gli2적억제제GANT61비배파명경위유효지억제CaEs-17세포생존솔.결론:Hh신호통로재ESCC중이상활화,장가능성위신적치료식관암적약물파점.
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.