Itraconazole Induces Apoptosis And Cell Cycle Arrest Via Inhibiting Hedgehog Signaling In Gastric Cancer Cells

Itraconazole has been used in the treatment research for varies of human cancer.To assess the effect of itraconazole on the Hedgehog(Hh)pathway and on tumor cells growth in human gastric tumors,we study it in vitro and in vivo.By studying the effect of itraconazole on gastric cancer cell proliferation,cycle and apoptosis,its act on gastric cancer cell biology is evaluated.To make sure whether Hh pathway is activated in human gastric cancer,the expression of Hh pathway is detected in human gastric cancer tissue samples.After having been treated by itraconazole,related molecular expression in Hh pathway is tested to illustrate whether itraconazole has influence on the Hedgehog pathway in gastric cancer cells.The results demonstrated that itraconazole could remarkably inhibit the growth of gastric cancer cells,which act by regulating the G1-S transition and inducing apoptosis of gastric cancer cells.Furthermore,itraconazole suppressed the proliferation of gastric cancer cells significantly when combination with 5-FU.In addition,Hh signaling was found to be abnormally activated in human gastric cancer samples.Importantly,the expression of glioma-associated zinc finger transcription factor 1(Gli1)was decreased no matter on the transcriptional or translational lever when treated with itraconazole.Moreover,dual luciferase assay showed that itraconazole could hinder the transcription of Gli1.Therefore,our data indicated that Hedgehog signaling is activated in human gastric tumor tissue and itraconazole can inhibit the growth of human gastric cancer cells by impacting on Hedgehog signaling.