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Acute promyelocytic leukemia (APL), characterized by the presence of the promyelocytic leukemia (PML)-retinoic acid α receptor (RARα) fusion protein, responds to treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, drug resistance and side effects restrict the application of these reagents. Hence, the development of novel therapeutic drugs for APL treatment is critical. Lapatinib, a small-molecule tyrosine kinase inhibitor, has been used in the treatment of different tumors. However, it is unclear whether lapatinib exerts antitumor effects on APL. The present study investigated the antitumor effects and potential mechanisms of lapatinib on NB4 cells derived from APL. Cell Counting Kit-8 assay and colony forming analysis indicated that lapatinib inhibited NB4 cell proliferation in a dose-dependent manner. Flow cytometry analysis revealed that lapatinib induced cell cycle arrest at the S phase and promoted cell apoptosis. Furthermore, Liu's staining and Hoechst 33258 staining revelaed that lapatinib treatment induced an apoptotic nuclear phenomenon. Furthermore, lapatinib induced apoptosis by decreasing Bcl-2 and PML-RARα levels, and by increasing the levels of Bax, cleaved PARP, cleaved caspase-3 and cleaved caspase-9. In addition, lapatinib increased the levels of phospho-p38 MAPK and phospho-JNK, and decreased the levels of phospho-Akt. The p38 inhibitor PD169316 partially blocked lapatinib-induced proliferation inhibition and apoptosis, whereas the JNK inhibitor SP600125 had no such effects. Therefore, treatment with lapatinib may be a promising strategy for APL therapy. [ABSTRACT FROM AUTHOR]

MicroRNAs have been shown to be involved in various cell processes, including proliferation, apoptosis and differentiation. However, little is known about their function in granulopoiesis. In the present study, overexpression and knockdown experiments revealed that miR-15b was required to block the proliferation of NB4 and HL60 cells and induce them differentiated to granulocyte lineage. Moreover, we identified CCNE1 as a direct target of miR-15b, and demonstrated that CCNE1 was involved in cell differentiation and proliferation in acute promyelocytic leukemia cells. In addition, we demonstrated a novel pathway in which miR-15b regulated cells arrested in the G0/G1 phase and promoted terminal differentiation of cells by targeting CCNE1, which could modulate the cell cycle effort pRb in APL cells. These events blocked cell proliferation and promoted granulocyte differentiation. In conclusion, our data highlighted, for the first time, the important role of miR-15b in myeloid differentiation and suggested the potential role of miR-15b in cancer therapy. • miR-15b has an important function in the differentiation and proliferation of acute promyelocytic leukemia. • miR-15b serves as a tumor suppressor by targeting CCNE1. • miR-15b may be a novel therapeutic strategy for APL in the future. [ABSTRACT FROM AUTHOR]