GANT61 as an inhibitor of Gli inhibits growth and invasion of esophageal adenocarcinoma / 天津医药

ABSTRACT

Objective To study the inhibitory effects of GANT61, as an inhibitor of Gli, on the growth of human esophageal adenocarcinoma cell lines OE19 and OE33, and their mechanisms thereof. Methods After treating with different concentrations of GANT61(30,20,13.333 3,8.888 8,5.925 9,3.950 6,2.633 7,1.755 8,1.170 5μmol/L),the cell viabilities of OE19 and OE33 were detected by MTS method, which expressed by IC50. The Gli1and Gli2 mRNA expressions treated with GANT61(10 μmol/L GANT61) or DMSO for 24 h were detected in OE19 and OE33 cell lines by real time fluorescence quantitative PCR. The protein expressions of Gli1, Gli2 and CyclinD1 treated with GANT61 or DMSO for 24 h were detected in OE19 and OE33 cell lines by Western blot assay. Transwell invasion assay was performed to evaluate the inhibiting effect on OE19 and OE33 cell invasion by the treatment of GANT61 or DMSO. Results The IC50 of GANT61 was 8.08μmol/L in OE19 and 9.65μmol/L in OE33 cells. Compared with DMSO group, Gli1 and Gli2 mRNA expressions and Gli1,Gli2 and CyclinD1 protein expressions were significantly decreased in OE19 and OE33 cells of GANT61 group (P<0.05). The number of penetrating cells was significantly reduced in OE19 and OE33 cells of GANT61 group compared with that of DMSO group (P<0.01). Conclusion GANT61 can inhibit the growth and invasion of esophageal neoplasms cells by down-regulating Gli1 and Gli2 mRNA expression,which indicates that Hedgehog signaling pathway may play an important role in carcinogenesis and progression of esophageal adenocarcinoma.