Figure 4
Figure 4. PMA inhibits proliferation and induces apoptosis of human CML cells. (A) FACS analysis showed that MSR1 protein was up-regulated in human leukemic cells treated with PMA for 48h compared with untreated cells. (B) PMA inhibits proliferation of human leukemic cells. K562 cells were treated with DMSO or PMA (80nM) for 48 and 96 hours, and live cells were counted (**P < .01). (C) PMA induces apoptosis of K562 cells. K562 cells were treated with DMSO or PMA (80nM) for 48 hours. Apoptotic cells (annexin V+/7AAD+) cells were analyzed by FACS (**P < .01). (D) PMA inhibits LSCs from CML mice in vitro. Bone marrow cells isolated from mice with CML induced by BCR-ABL-GFP were cultured (2 × 106 cells/6 cm plate) under stem cell conditions in the presence of DMSO, imatinib (1μM) or PMA (80nM) for 3 days, followed by FACS analysis of LSCs (*P < .05, **P < .01). (E) Bone marrow cells from recipients of BCR-ABL–transduced bone marrow cells from Msr1−/− donor mice were treated with PMA (80nM) for 3 days. The total number LSCs at the end of the culture were calculated based on FACS analysis and total cell counts.

PMA inhibits proliferation and induces apoptosis of human CML cells. (A) FACS analysis showed that MSR1 protein was up-regulated in human leukemic cells treated with PMA for 48h compared with untreated cells. (B) PMA inhibits proliferation of human leukemic cells. K562 cells were treated with DMSO or PMA (80nM) for 48 and 96 hours, and live cells were counted (**P < .01). (C) PMA induces apoptosis of K562 cells. K562 cells were treated with DMSO or PMA (80nM) for 48 hours. Apoptotic cells (annexin V+/7AAD+) cells were analyzed by FACS (**P < .01). (D) PMA inhibits LSCs from CML mice in vitro. Bone marrow cells isolated from mice with CML induced by BCR-ABL-GFP were cultured (2 × 106 cells/6 cm plate) under stem cell conditions in the presence of DMSO, imatinib (1μM) or PMA (80nM) for 3 days, followed by FACS analysis of LSCs (*P < .05, **P < .01). (E) Bone marrow cells from recipients of BCR-ABL–transduced bone marrow cells from Msr1−/− donor mice were treated with PMA (80nM) for 3 days. The total number LSCs at the end of the culture were calculated based on FACS analysis and total cell counts.

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