Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells
Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells
复制标题
骨肉瘤患者临床病例报告及毛蕊异黄酮对人骨肉瘤细胞的抗癌作用
DOI：
10.1002/jcb.28360
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发表时间：
2019-06-01
影响因子：
4
通讯作者：
Zhang, Jianfeng
中科院分区：
文献类型：
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作者：
Qiu, Rubiao;Ma, Gang;Zhang, Jianfeng
骨肉瘤（OS）是骨骼中的恶性肿瘤，其特征是青少年的主要发生。生物活性化合物（CC）发现对癌症发挥有效的药理作用。我们先前的研究表明，CC对抗OS效应的好处。但是，需要研究此动作背后的进一步分子机制。在这项研究中，收集了人类OS样品和临床数据，并用于进一步测试和分析。此外，分别通过一系列生化方法和免疫测定法分别使用人骨肉瘤细胞系（143b）和肿瘤 - Xenogroght裸鼠评估CC的抗塑性活性。与非OS对照相比，人类OS样品显示肿瘤microRNA-223（miR-223）和NF-BP65（肿瘤细胞IB蛋白）的表达升高。在细胞培养研究中，经CC处理的143B细胞显示细胞生长降低，乳酸脱氢酶（LD）含量增加以及细胞miR-223水平下调。在CC处理中，增殖细胞核抗原，B细胞淋巴瘤2（BCL-2），聚（ADP-核糖）聚合酶（PARP）的免疫标记细胞依赖性降低剂量，而CASPase-3阳性细胞则升高。此外，CC处理的细胞中NF-BP65的蛋白质表达下调。此外，肿瘤 - Xenogrograpt Nude小鼠随后进行CC治疗表现出肿瘤质量，miR-223水平和Bcl-2水平的降低，PARP阳性细胞，以及NF-BP65的下降，在OS样品中IB蛋白表达。综上所述，这些实验发现表明，CC通过诱导凋亡和抑制肿瘤细胞中的miR-223-IB信号传导途径表现出对OS的潜在药理活性。
Osteosarcoma (OS) is a malignant neoplasia in bone, characterized with main occurrence in teenagers. Calycosin (CC), a bioactive compound, is found to play potent pharmacological effects against cancer. Our previous study indicates CC-exerted benefits for anti-OS effect. However, further molecular mechanism behind this action needs to be investigated. In this study, human OS samples and clinical data were collected and used for further test and analysis. In addition, human osteosarcoma cell line (143B) and tumor-xenograft nude mice were used to evaluate antineoplastic activities of CC through a series of biochemical methods and immunoassays, respectively. Compared with non-OS controls, human OS samples showed increased levels of neoplastic microRNA-223 (miR-223), and elevated expressions of NF-Bp65, IB proteins in tumor cells. In cell culture study, CC-treated 143B cells showed reduced cell growth, increased lactic dehydrogenase (LD) content, and downregulated cellular miR-223 level. Immunolabeled cells of proliferating cell nuclear antigen, B-cell lymphoma 2 (Bcl-2), poly(ADP-ribose) polymerase (PARP) in CC treatments were decreased dose-dependently, while caspase-3 positive cells were elevated. Further, protein expressions of NF-Bp65, IB in CC-treated cells were downregulated. In addition, tumor-xenograft nude mice followed by CC treatments exhibited reductions of tumor mass, miR-223 levels, and Bcl-2, PARP-positive cells, as well as downregulations of NF-Bp65, IB protein expressions in OS samples. Taken together, these experimental findings reveal that CC exhibits potential pharmacological activities against OS through inducing apoptosis and inhibiting miR-223-IB signaling pathway in neoplastic cells.