JQ1 Inhibits Proliferation and Induces Apoptosis of Leukemia Cells Through BCL-2 Regulated Pathway

Abstract Objective To explore the mechanism of JQ1 on leukemia cells. Methods This study takes two myeloid leukemia cell lines as a research model. Cells treated with high concentration of JQ1 were collected for quantitative real-time PCR, immunoblot and flow cytometry to verify the effects of JQ1 on myeloid leukemia tumor cells. Combined with mRNA sequencing of cell lines to identify the differences in mRNA expression of different cell lines. Results Two cell lines changed cell morphology under JQ1 treatment. The cell membrane appeared in varying degrees of wrinkled internal subsidence. K562 cell lines can maintain stable proliferation after being induced by a specific concentration of JQ1. However, JQ1 cannot induce the death of the K562 cells. Although the MYC and BCL2 gene expression decreased, JQ1 did not affect the c-Myc targeted genes to affect the cell cycle, nor did it trigger the BCL2-mediated apoptosis pathway. On the contrary, after JQ1 induced the MV-4-11 cells, the MYC-mediated cell cycle significantly slowed down and arrested at the G0/G1 phase. The death of MV-4-11 tumor cells through the apoptosis pathway regulated by BCL-2 family. Conclusion JQ1 has different pharmacological effects on two myeloid leukemia cell lines. For MV-4-11, JQ1 mainly inhibited cell cycle by regulating MYC pathway and induced BCL-2-mediated apoptosis to kill myeloid leukemia tumor cells and thus perform anti-tumor effects. K-562 cells showed drug resistance to JQ1 which confirmed that the K-562 cell line has a feedback mechanism that prevents JQ1-induced apoptosis.