研究动态
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多功能聚乙烯亚胺笼式铂纳米簇通过调节 BAX-Bcl-2/Caspase-3/PARP 轴促进骨肉瘤细胞凋亡。

Multiproperty Polyethylenimine-Caged Platinum Nanoclusters Promote Apoptosis of Osteosarcoma Cells via Regulating the BAX-Bcl-2/Caspase-3/PARP Axis.

发表日期:2023 Oct 13
作者: Jialin Wang, Mengjun Zhang, Xin Huang, Haodi Yue
来源: MOLECULAR PHARMACEUTICS

摘要:

骨肉瘤是儿童中常见的原发性骨癌,由于耐药性高,预后较差。本研究的目的是研究荧光超细聚乙烯亚胺涂层笼状铂纳米团簇 (PEI-Pt NC) 作为骨肉瘤抗肿瘤药物的潜力。本研究的主要重点涉及利用骨肉瘤细胞(U2-OS 和 MG-63)和正常对照细胞(hBMSC)作为主要研究对象。通过共聚焦显微镜观察 PEI-Pt NC 进入骨肉瘤细胞的能力。通过利用各种方法评估 PEI-Pt NC 对迁移和增殖的影响,包括 CCK8 测定、Ki-67 免疫荧光、克隆形成测定、transwell 测定和伤口愈合测定。此外,通过流式细胞术和Western blotting技术探讨了PEI-Pt NCs对细胞凋亡的影响及其潜在机制。 PEI-Pt NCs 表现出进入骨肉瘤细胞(包括细胞核)的能力,同时还表现出荧光标记特性。此外,PEI-Pt NCs 有效阻止骨肉瘤细胞的迁移和增殖。此外,PEI-Pt NCs 通过调节 BAX-Bcl-2/Caspase 3/PARP 轴促进细胞凋亡。新型纳米材料PEI-Pt NCs具有多种优势功能,包括阻碍细胞增殖和迁移的能力,以及调节BAX-Bcl-2/Caspase 3/PARP轴,从而促进细胞凋亡的能力。因此,这种纳米材料在解决骨肉瘤铂基治疗不足的问题方面表现出巨大的潜力。
Osteosarcoma, a prevalent primary bone cancer in children, exhibits a poor prognosis due to the high prevalence of drug resistance. The objective of this study was to investigate the potential of fluorescent ultrafine polyethylenimine-coated caged platinum nanoclusters (PEI-Pt NCs) as an antitumor agent in osteosarcoma. The primary focus of this study involved the utilization of osteosarcoma cells (U2-OS and MG-63) and normal control cells (hBMSC) as the primary subjects of investigation. The capacity of PEI-Pt NCs to enter osteosarcoma cells was observed through the implementation of confocal microscopy. The impact of PEI-Pt NCs on migration and proliferation was assessed through the utilization of various methodologies, including the CCK8 assay, Ki-67 immunofluorescence, clone formation assay, transwell assay, and wound healing assay. Furthermore, the influence of PEI-Pt NCs on apoptosis and its underlying mechanism was explored through the implementation of flow cytometry and Western blotting techniques. The PEI-Pt NCs demonstrated the capability to enter osteosarcoma cells, including the nucleus, while also exhibiting fluorescent labeling properties. Furthermore, the PEI-Pt NCs effectively impeded the migration and proliferation of osteosarcoma cells. Additionally, the PEI-Pt NCs facilitated apoptosis by modulating the BAX-Bcl-2/Caspase 3/PARP axis. The novel nanomaterial PEI-Pt NCs possess diverse advantageous capabilities, including the ability to impede cell proliferation and migration, as well as the capacity to modulate the BAX-Bcl-2/Caspase 3/PARP axis, thereby promoting cell apoptosis. Consequently, this nanomaterial exhibits promising potential in addressing the issue of inadequate platinum-based treatment for osteosarcoma.