Guangxi Maternal and Child Health Hospital, Guangxi Zhuang Autonomous Region, P. R. China.
Department of Cutaneous Surgery, Burns Centre PLA, Xijing Hospital Fourth Military Medical University, Xijing, Shaanxi Province, P. R. China.
J Cell Biochem. 2019 Jun;120(6):10697-10706. doi: 10.1002/jcb.28360. Epub 2019 Jan 16.
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-κBp65, IκBα 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-κBp65, IκBα 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-κBp65, IκBα 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-IκBα signaling pathway in neoplastic cells.
骨肉瘤(OS)是一种骨恶性肿瘤,主要发生在青少年。毛蕊异黄酮(CC)是一种生物活性化合物,具有抗肿瘤作用。我们之前的研究表明 CC 对 OS 具有治疗作用。然而,其作用机制尚需进一步研究。本研究收集了人骨肉瘤标本和临床资料,进一步检测和分析。此外,通过一系列生化方法和免疫检测,分别用人骨肉瘤细胞系(143B)和肿瘤异种移植裸鼠评估 CC 的抗肿瘤活性。与非 OS 对照组相比,人骨肉瘤组织样本中肿瘤细胞的癌性 microRNA-223(miR-223)水平升高,NF-κBp65、IκBα 蛋白表达升高。在细胞培养研究中,CC 处理的 143B 细胞表现出细胞生长减少、乳酸脱氢酶(LD)含量增加和细胞内 miR-223 水平下调。CC 处理的增殖细胞核抗原、B 细胞淋巴瘤 2(Bcl-2)、多聚(ADP-核糖)聚合酶(PARP)免疫标记细胞呈剂量依赖性减少,而 caspase-3 阳性细胞增加。此外,CC 处理细胞的 NF-κBp65、IκBα 蛋白表达下调。另外,经 CC 处理的肿瘤异种移植裸鼠的肿瘤质量、miR-223 水平、Bcl-2、PARP 阳性细胞减少,以及 OS 组织中 NF-κBp65、IκBα 蛋白表达下调。综上所述,这些实验结果表明,CC 通过诱导细胞凋亡和抑制肿瘤细胞中 miR-223-IκBα 信号通路,发挥对 OS 的潜在药理作用。