GANT61诱导食管鳞癌细胞凋亡的作用及其机制

目的 研究Gli抑制剂GANT61诱导人食管鳞癌细胞OE21和KYSE-30凋亡的机制。方法 应用不同浓度（0、10、15 μmol/L）的GANT61处理OE21和KYSE-30细胞24 h后，Western blot观察GANT61作用于OE21和KYSE-30细胞后对Gli1、Gli2、Fas和Bcl-2蛋白表达的影响。流式细胞术观察细胞凋亡及Fas、Bcl-2蛋白的表达。结果 Western blot显示GANT61可以剂量依赖性显著下调OE21和KYSE-30细胞Gli1、Gli2和Bcl-2蛋白表达，增加Fas蛋白表达。流式细胞术检测显示不同浓度GANT61作用24 h后，OE21和KYSE-30细胞表现出不同程度的细胞凋亡并且呈药物剂量依赖性，与空白对照组相比差异均有统计学意义（P=0.000）；与空白对照组相比，OE21和KYSE-30细胞中Bcl-2蛋白表达水平显著降低且呈药物剂量依赖性，差异均有统计学意义（P=0.000）； Fas蛋白表达水平显著增加且呈药物剂量依赖性，差异均有统计学意义（P=0.000）。结论 GANT61明显诱导细胞凋亡，其作用机制可能与其通过特异性抑制OE21和KYSE-30细胞中Gli1、Gli2表达从而调节Fas和Bcl-2蛋白表达有关。

Effect of GANT61 on Apoptosis of Esophageal Squamous Carcinoma Cells and Its Mechanism

Objective To investigate the effect of GANT61 on the apoptosis of esophageal squamous carcinoma cells OE21 and KYSE-30, and to explore its possible mechanism. Methods After OE21 and KYSE-30 cell lines were treated with different concentrations（0, 10, 15μmol/L）of GANT61 for 24h, the protein expression of Gli1, Gli2, Fas and bcl-2 were detected by Western blot. Cell apoptosis, Fas and bcl-2 expression levels of OE21 and KYSE-30 cell lines were measured by flow cytometry. Results Western blot assay showed that GANT61 decreased Gli1, Gli2, Bcl-2 protein expression and increased Fas protein expression in a dose-dependent manner. Compared with DMSO group, the apoptotic rates of OE21 and KYSE-30 cell lines were significantly increased in a dose-dependent manner(P=0.000); the Bcl-2 protein expression levels were significantly decreased in a dose-dependent manner(P=0.000); the Fas protein expression levels were significantly increased in a dose-dependent manner(P=0.000). Conclusion GANT61 could enhance the apoptotic rates of OE21 and KYSE-30 cells, and this effect may be associated with GANT61 decreasing Gli1 and Gli2 expression to regulate Fas and Bcl-2 protein expression levels in esophageal squamous carcinoma cells.