title: β-Catenin and AKT are promising targets for combination therapy in acute myeloid leukemia.
abstract: In this study, we confirmed that combining HHT with ACR can result in synergistic cytotoxicity to AML cells in vitro and in vivo. Combining HHT and ACR simultaneously inhibited PI3K/AKT and WNT/β-catenin signaling in AML cells. Significant increases in growth inhibition and apoptosis were induced by an AKT inhibitor when the WNT3A gene of THP-1 cells was silenced. HHT+ACR could synergistically induce the apoptosis of CD34(+)/CD38(-) primary AML cells. These results highlight β-catenin and AKT are promising targets for combination therapy for AML.
authors.affiliation: Department of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: L-S
authors.initials: LS
authors.lastname: You
authors.forename: W-M
authors.initials: WM
authors.lastname: Ni
authors.forename: Q-L
authors.initials: QL
authors.lastname: Ma
authors.forename: Y
authors.initials: Y
authors.lastname: Tong
authors.forename: L-P
authors.initials: LP
authors.lastname: Mao
authors.forename: J-J
authors.initials: JJ
authors.lastname: Qian
authors.forename: J
authors.initials: J
authors.lastname: Jin
mesh_terms: D015250:Aclarubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D020868:Gene Silencing; D005947:Glucose / Q000378:metabolism; D006248:Harringtonines / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000077863:Homoharringtonine; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D006248:Harringtonines; D019253:Proto-Oncogene Proteins c-bcl-2; D051153:Wnt Proteins; D051176:beta Catenin; D000077863:Homoharringtonine; D015250:Aclarubicin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D005947:Glucose
keywords: Aclarubicin; Acute myeloid leukemia; Homoharringtonine; Synergistic; β-Catenin