title: Growth inhibition of imatinib-resistant CML cells with the T315I mutation and hypoxia-adaptation by AV65--a novel Wnt/β-catenin signaling inhibitor.
abstract: We investigated the effect of a novel Wnt/β-catenin signaling inhibitor, AV65 on imatinib mesylate (IM)-sensitive and -resistant human chronic myeloid leukemia (CML) cells in vitro. AV65 inhibited the proliferation of various CML cell lines including T315I mutation-harboring cells. AV65 reduced the expression of β-catenin in CML cells, resulting in the induction of apoptosis. Moreover, AV65 inhibited the proliferation of hypoxia-adapted primitive CML cells that overexpress β-catenin. The combination of AV65 with IM had a synergistic inhibitory effect on the proliferation of CML cells. These findings suggest that AV65 could be a novel therapeutic agent for the treatment of CML.
authors: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
authors: Rina
authors: R
authors: Nagao
authors: Eishi
authors: E
authors: Ashihara
authors: Shinya
authors: S
authors: Kimura
authors: Jeffrey W
authors: JW
authors: Strovel
authors: Hisayuki
authors: H
authors: Yao
authors: Miki
authors: M
authors: Takeuchi
authors: Ruriko
authors: R
authors: Tanaka
authors: Yoshihiro
authors: Y
authors: Hayashi
authors: Hideyo
authors: H
authors: Hirai
authors: Janak
authors: J
authors: Padia
authors: Kathryn
authors: K
authors: Strand
authors: Taira
authors: T
authors: Maekawa
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides; D048708:Cell Growth Processes / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C495270:CTNNB1 protein, human; D010879:Piperazines; D011743:Pyrimidines; D051153:Wnt Proteins; D051176:beta Catenin; D000068877:Imatinib Mesylate