title: Gli inhibitor GANT61 causes apoptosis in myeloid leukemia cells and acts in synergy with rapamycin.
abstract: Aberrant reactivation of Gli signaling has been described in a wide variety of human cancers and rapamycin can down-regulate Gli pathway in some solid tumors. In this study, we attempt to define the cytotoxic effect of Gli inhibitor on AML cells. And the regulation action of rapamycin on Gli in AML cells also has been assessed. Gli inhibitor GANT61 caused growth arrest and apoptosis in AML cells. Rapamycin decreased not only the Gli protein and mRNA expressions but also expression of the Gli-luciferase reporter in AML cells. Synergism effect between GANT61 and rapamycin was found in Kasumi-1, HL-60 and U937 cell lines. The results suggest that aberrant Gli activation is a feature of some myeloid leukemic cells and Gli activiation can be down-regulated by rapamycin.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Pan
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.forename: Yazhu
authors.initials: Y
authors.lastname: Wang
authors.forename: Pingping
authors.initials: P
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D020298:U937 Cells; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000071676:Zinc Finger Protein GLI1
chemical_list: D000970:Antineoplastic Agents; C551027:GANT 61; C400551:GLI1 protein, human; D011725:Pyridines; D011743:Pyrimidines; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; D020123:Sirolimus; C000541:cyclopamine