A novel mesenchymal stem cell-based regimen for acute myeloid leukemia differentiation therapy

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Combination of artemether with etoposide inhibits cell proliferation and invasion in small cell lung cancer cell line H446 / 中国药科大学学报

This study was to investigate the inhibitory effects of artemether in combination with etoposide on the proliferation and invasion ability of human small cell lung cancer cell line H446.H446 cells were treated with different concentrations of artemether or etoposide alone or their combination.The inhibitory effects on proliferation were detected by MTT assay,while cell cycle and apoptosis of H446 cells in each group were analyzed by flow cytometry using PI and Annexin V/PI-staining,respectively.The invasion capability of H446 cells in different groups was tested with matrigel-coated transwell.The results implicated that artemether or etoposide or their combination does inhibit proliferation of H446 cells dose-dependently.Artemether alone had little effect on the apoptosis of H446 cells while its combination with etoposide resulted in significantly apoptosis of H446 cells comparing with other groups (P ＜ 0.05).Etoposide blocked H446 progression markedly by arresting cell cycle in G2 phase with percentage of cells in G1 phase decreasing significantly while artemether alone or in combination with etoposide had little synergetic effect on cell cycle.Artemether or etoposite alone or their combination could dramatically inhibit the invasion ability of H446 cells.