| Abstrakt: |
Background: The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM. Methods and results: hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line. The results were obtained from MTT, cell proliferation, cell cycle, and RT-qPCR evaluations. In the current study, we found that the proliferation effects of AML-derived exosomes relied on the dose and the time, and the optimal effects of exosomes were seen in 50 μg/ml, 48 h treatment. Flow cytometry analysis revealed a significant increase in the G1 phase, showing a 1.6-fold change compared to the control group (p value < 0.0001). RT-qPCR results demonstrated a significant upregulation of CCND1 (3.3-fold, p value < 0.0001), CDK4 (3.7-fold, p value < 0.0001), CDK6 (3.3-fold, p value < 0.0001), RAS (3.2-fold, p value < 0.0001), and Erk (3.4-fold, p value < 0.0001) expression levels, along with increased Ki-67 (2.6-fold, p value < 0.0001) levels. Moreover, treatment with 50 μg/ml, 48 h of AML-derived exosomes resulted in a notable reduction in BM-MSC apoptosis both in early (p value < 0.0001) and late (p value < 0.0001) apoptosis rate compared to control group. Conclusions: The findings will be of interest to AML-derived exosomes, which were able to potentiate the activation of the signaling pathways involved in the survival and proliferation of hBM-MSCs. Our findings suggest their specific targeting as a potential therapeutic strategy against cancer progression and metastasis. [ABSTRACT FROM AUTHOR] |
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