Ghorban Khan Tafreshi Mostafa, Mazaheri Zohreh, Heidari Mansour, Babaei Nahid, Doosti Abbas
Department of Molecular Cell Biology and Genetics, Bushehr Branch, Islamic Azad University, Bushehr, Iran .
Int J Mol Cell Med. 2021 Fall;10(4):265-275. doi: 10.22088/IJMCM.BUMS.10.4.265. Epub 2022 Jun 6.
Transforming growth factor-beta (TGF-β) plays a significant role in tumorigenesis. MiR-181b is a multifunctional miRNA involved in numerous cellular processes, such as cell fate and cell invasion. This study aimed to examine whether the co-culture of adipose-derived stem cells (ADSCs), highly expressing bone morphogenetic protein-4, with the U937 cell line, which is a human myeloid leukemia cell line, is able to induce cell death in this cancer cell line, considering the potential ability of ADSCs to migrate from tumor sites. Cell surface markers, namely CD73 and CD105, were analyzed to verify the identity of mesenchymal stem cells isolated from adipose tissue. Besides, the osteogenic and adipogenic differentiation potentials of ADSCs were evaluated. The induction of cell death and apoptosis in the U937 cell line was assessed using MTT and annexin V/ PI assays, respectively. The expression levels of miR-181 and were determined in the co-culture system using real-time PCR. The results of MTT and annexin V/ PI assays showed that BMP4-expressing ADSCs could inhibit cell viability and induce apoptosis in U937 cells in the co-culture system. The co-culture of ADSCs, highly expressing BMP-4, with the U937 cell line led to the downregulation of miR-181 and genes in the human cancer cell line. ADSCs may further be studied as a candidate for the treatment of hematological cancers.
转化生长因子-β（TGF-β）在肿瘤发生过程中起着重要作用。MiR-181b是一种多功能的微小RNA，参与众多细胞过程，如细胞命运和细胞侵袭。考虑到脂肪来源干细胞（ADSCs）从肿瘤部位迁移的潜在能力，本研究旨在探讨高表达骨形态发生蛋白-4的ADSCs与人类髓系白血病细胞系U937细胞系共培养是否能够诱导该癌细胞系发生细胞死亡。分析细胞表面标志物CD73和CD105，以验证从脂肪组织分离的间充质干细胞的身份。此外，还评估了ADSCs的成骨和成脂分化潜能。分别使用MTT法和膜联蛋白V/碘化丙啶（PI）法评估U937细胞系中细胞死亡和凋亡的诱导情况。使用实时聚合酶链反应（PCR）在共培养系统中测定miR-181和[此处原文缺失部分内容]的表达水平。MTT法和膜联蛋白V/PI法的结果表明，在共培养系统中，表达骨形态发生蛋白4的ADSCs可抑制U937细胞的活力并诱导其凋亡。高表达骨形态发生蛋白-4的ADSCs与U937细胞系共培养导致人类癌细胞系中miR-181和[此处原文缺失部分内容]基因的表达下调。ADSCs作为血液系统恶性肿瘤治疗的候选者可能需要进一步研究。
