title: Wnt5a enhances the response of CML cells to Imatinib Mesylate through JNK activation and γ-catenin inhibition.
abstract: Imatinib Mesylate is widely used for the treatment of chronic myelogenous leukaemia (CML), and its effects on CML cells are influenced by several signalling proteins. The research is aimed at determining whether Wnt5a affects the effects of Imatinib Mesylate against BCR-ABL positive CML cells (K562 cells and KU812 cells) and which signalling proteins are involved in. The results showed that Wnt5a augmented the effects of Imatinib Mesylate on inhibiting CML cells proliferation and inducing apoptosis in vitro; Wnt5a enhanced the inhibition effect of Imatinib Mesylate on the growth of K562 cells xenograft tumour in an animal model. Furthermore, Wnt5a inhibited β-catenin and its target gene Survivin, increased the activity of JNK and suppressed γ-catenin expression. When inhibiting the activity of JNK, the influence of Wnt5a on the effects of Imatinib Mesylate was attenuated. Moreover, JNK suppressed β-catenin and its target gene Survivin, and enhanced the effects of Imatinib Mesylate. These results suggest that Wnt5a can enhance the efficacy of Imatinib Mesylate through JNK/β-catenin/Survivin and γ-catenin/β-catenin/Survivin pathways.
authors: Department of Clinical Hematology, Third Military Medical University, Chongqing 400038, China.
authors: Chang-Chun
authors: CC
authors: Niu
authors: Chen
authors: C
authors: Zhao
authors: Xiao-Li
authors: XL
authors: Zhang
authors: Jing
authors: J
authors: Pan
authors: Chen
authors: C
authors: Zhao
authors: Wei-Ru
authors: WR
authors: Wu
authors: Zhi-Qiang
authors: ZQ
authors: Li
authors: Tao
authors: T
authors: Liu
authors: Zhong
authors: Z
authors: Yang
authors: Wei-Ke
authors: WK
authors: Si
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D051185:gamma Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051185:gamma Catenin; D000068877:Imatinib Mesylate; D048670:MAP Kinase Kinase 4
keywords: Chronic myeloid leukaemia; Imatinib Mesylate; JNK; Wnt5a; β-Catenin; γ-Catenin