CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Effect of human bone marrow mesenchymal stem cell-derived microvesicles on the apoptosis of the multiple myeloma cell line U266.
Effect of human bone marrow mesenchymal stem cell-derived microvesicles on the apoptosis of the multiple myeloma cell line U266.
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我们的研究结果凸显了 BMSC-MVs 对多发性骨髓瘤细胞系 U266 的治疗获益，并表明微囊泡可能具有治疗优势。
微囊泡是不同类型细胞产生的膜性颗粒，近期开始被研究用于抗癌。本研究旨在调查人骨髓间充质干细胞来源微囊泡（BMSC-MV）对多发性骨髓瘤细胞系 U266 的作用。通过超速离心从骨髓间充质干细胞中分离 BMSC-MV，并使用透射电子显微镜（TEM）和动态光散射（DLS）进行表征。以 15、30、60 和 120 μg/mL 的 BMSC-MV 处理 U266 细胞 3 天和 7 天，分别通过 MTT 法、乳酸脱氢酶（LDH）法和 8-羟基-2′-脱氧鸟苷（8-OHdG）测定，考察细胞存活、细胞毒性及 DNA 损伤。此外，通过流式细胞术评估 60 μg/mL BMSC-MV 处理后第 7 天 U266 细胞的凋亡率。最后采用 qRT-PCR 检测 60 μg/mL BMSC-MV 处理后第 7 天 U266 细胞中 BCL2、BAX 和 CCND1 的表达水平。
BMSC-MV 平均粒径约 410 nm。MTT 和 LDH 检测显示，BMSC-MV 处理降低了 U266 细胞存活率，并对其产生细胞毒作用。处理后 8-OHdG 水平升高，表明 DNA 损伤随剂量增加。BMSC-MV 处理的 U266 细胞在第 7 天凋亡率也升高。处理细胞中 BCL2 和 CCND1 表达降低，而 BAX 表达呈上升趋势。
研究结果凸显 BMSC-MV 对多发性骨髓瘤细胞系 U266 的治疗获益，表明微囊泡可能具有治疗价值。未来体内研究可进一步验证这些发现。
Microvesicles are membraned particles produced by different types of cells recently investigated for anticancer purposes. The current study aimed to investigate the effects of human bone marrow mesenchymal stem cell-derived microvesicles (BMSC-MVs) on the multiple myeloma cell line U266. BMSC-MVs were isolated from BMSCs via ultracentrifugation and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U266 cells were treated with 15, 30, 60, and 120 g/mL BMSC-MVs for three and seven days and the effects of treatment in terms of viability, cytotoxicity, and DNA damage were investigated via the MTT assay, lactate dehydrogenase (LDH) assay, and 8 hydroxy-2'-deoxyguanosine (8 OHdG) measurement, respectively. Moreover, the apoptosis rate of the U266 cells treated with 60 g/mL BMSC-MVs was also assessed seven days following treatment via flow cytometry. Ultimately, the expression level of BCL2, BAX, and CCND1 by the U266 cells was examined seven days following treatment with 60 g/mL BMSC-MVs using qRT-PCR.
BMSC-MVs had an average size of ~ 410 nm. According to the MTT and LDH assays, BMSC-MV treatment reduced the U266 cell viability and mediated cytotoxic effects against them, respectively. Moreover, elevated 8 OHdG levels following BMSC-MV treatment demonstrated a dose-dependent increase of DNA damage in the treated cells. BMSC-MV-treated U266 cells also exhibited an increased apoptosis rate after seven days of treatment. The expression level of BCL2 and CCND1 decreased in the treated cells whereas the BAX expression demonstrated an incremental pattern.
Our findings accentuate the therapeutic benefit of BMSC-MVs against the multiple myeloma cell line U266 and demonstrate how microvesicles could be of therapeutic advantage. Future in vivo studies could further corroborate these findings.
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