期刊
ANTICANCER RESEARCH
卷 37, 期 11, 页码 6047-6053出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.12052
关键词
BMI1; leukemia; NOTCH; CDKN2A
类别
资金
- Japan Society for the Promotion of Science [26460669]
Background/Aim: B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is up-regulated in several cancers; therefore, we investigated the effects of BMI1 inhibitors on leukemia cells. Materials and Methods: Four acute myeloid leukemia and two T-lymphoblastic leukemia cell lines were treated with BMI1 inhibitors artemisinin, PRT4165, and PTC-209 and analyzed for cell proliferation and gene expression by microarray and immunoblotting. Results: PTC-209 and PRT4165 suppressed the growth of all cell lines through apoptosis. Artemisinin acted only on Jurkat cells. BMI1 inhibitors and BMI1-specific siRNA down-regulated the expression of NOTCH signaling proteins NOTCH1, HES1, and MYC. All but one cell lines did not have the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene targeted by BMI1, thus the inhibitors acted through CDKN2A-independent pathways. Conclusion: BMI1 inhibition suppressed proliferation of leukemia cells through NOTCH signaling which functions downstream of BMI1, suggesting that BMI1 inhibitors can be candidate targeted drugs against leukemia.
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