Nikravesh Fariba, Arezoomand Hossein, H Mirzaee Khalilabadi Roohollah, Nooshadokht Maryam, Mardani Valandani Hajar
Department of Hematology and Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Department of Medical Parasitology and Mycology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Bioimpacts. 2024 Oct 29;15:30454. doi: 10.34172/bi.30454. eCollection 2025.
The current understanding highlights the intricate relationship between leukemic cells and their microenvironment, emphasizing the significant impact of environmental factors on chemotherapy resistance or sensitivity. Platelet-derived microparticles (PMPs) play a crucial role in facilitating intercellular communication, significantly contributing to the complex dynamics of cancer pathology and treatment outcomes. This study aims to investigate the cytotoxic and apoptotic effects of PMP, Ara-C, and their combinations on cancer cells, as well as their influence on the expression of critical genes like and in the context of Acute Lymphoblastic Leukemia (ALL) cell line (Nalm-6).
PMPs were isolated through centrifugation at varying speeds, and their concentration was determined using the BCA assay. The size and immunophenotypic characteristics of PMPs were analyzed using dynamic light scattering (DLS) and flow cytometry. The cytotoxic and apoptotic effects of PMP, Ara-C, and their combinations on Nalm-6 cells were assessed using the MTT assay, the trypan blue exclusion assay, and flow cytometry. Gene expression levels were analyzed using real-time PCR.
According to our research findings, PMPs did not independently impact the viability and apoptosis of Nalm-6 cells; however, they synergistically augmented Ara-C's suppressive impact on viability and apoptosis. The MTT assay showed that both PMPs and Ara-C, whether administered alone or in combination, had a cytotoxic effect on the Nalm-6 cells. Furthermore, the combined treatment significantly affected the expression of and genes.
Our study demonstrates that PMPs have the potential to improve the effectiveness of Ara-C chemotherapy in treating ALL. These findings contribute to a deeper understanding of the interplay between PMP and chemotherapy agents, offering potential insights for optimizing treatment strategies and improving patient outcomes in ALL.
当前的认识突出了白血病细胞与其微环境之间的复杂关系，强调了环境因素对化疗耐药性或敏感性的重大影响。血小板衍生微粒（PMPs）在促进细胞间通讯中起关键作用，对癌症病理和治疗结果的复杂动态有显著贡献。本研究旨在探讨PMP、阿糖胞苷（Ara-C）及其组合对癌细胞的细胞毒性和凋亡作用，以及它们在急性淋巴细胞白血病（ALL）细胞系（Nalm-6）背景下对关键基因如 和 表达的影响。
通过不同速度离心分离PMPs，并使用BCA测定法测定其浓度。使用动态光散射（DLS）和流式细胞术分析PMPs的大小和免疫表型特征。使用MTT测定法、台盼蓝排斥测定法和流式细胞术评估PMP、Ara-C及其组合对Nalm-6细胞的细胞毒性和凋亡作用。使用实时PCR分析基因表达水平。
根据我们的研究结果，PMPs并未独立影响Nalm-6细胞的活力和凋亡；然而，它们协同增强了Ara-C对活力和凋亡的抑制作用。MTT测定法表明，PMPs和Ara-C单独或联合使用均对Nalm-6细胞有细胞毒性作用。此外，联合治疗显著影响了 和 基因的表达。
我们的研究表明，PMPs有潜力提高Ara-C化疗治疗ALL的有效性。这些发现有助于更深入地理解PMP与化疗药物之间的相互作用，为优化ALL的治疗策略和改善患者预后提供潜在见解。
