title: The synergistic killing of AML cells co-cultured with HS-5 bone marrow stromal cells by As2O3 and the PI3K/Akt signaling pathway inhibitor LY294002.
abstract: We aimed to investigate whether a combination of resistance to arsenic trioxide (As2O3) and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway inhibitor LY294002 can inhibit the proliferation of AML cells in the bone marrow microenvironment. Three AML cell lines were grown with HS-5 human bone marrow stromal cells in adherent co-cultures. The inhibitory effects of As2O3 alone or in combination with LY294002 on the proliferation of these co-cultured AML cells were observed. The PI3K/Akt signaling pathway was detected by Western Blot in co-cultured AML cells cultured alone or treated with As2O3 alone or in combination with LY294002. Our results demonstrate that AML cells adhered to stroma exhibited significantly reduced sensitivity to As2O3. The resistance can be partially abolished by inhibiting the PI3K/Akt pathway. The administration of As2O3 in combination with a PI3K/Akt signaling pathway inhibitor may be expected to become a new approach to the treatment of AML.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Juanying
authors.initials: J
authors.lastname: Wu
authors.forename: Qin
authors.initials: Q
authors.lastname: Yuan
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.forename: Huifang
authors.initials: H
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D018920:Coculture Techniques; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects*; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D010087:Oxides; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051058:Oncogene Protein v-akt; D000077237:Arsenic Trioxide