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Clinical case report of patients with osteosarcoma and anticancer benefit of calycosin against human osteosarcoma cells
Authors:Rubiao Qiu  Gang Ma  Xueyu Li  Qunfeng Shi  Xinning Li  Xiong Zhou  Yuanyuan Tang  Zhaodi Xie  Shijie Liao  Yiwu Qin  Ruyue Wang  Yu Ye  Jiefeng Luo  Jianfeng Zhang
Institution:1. Guangxi Maternal and Child Health Hospital, Guangxi Zhuang Autonomous Region, P. R. China;2. Department of Cutaneous Surgery, Burns Centre PLA, Xijing Hospital Fourth Military Medical University, Xijing, Shaanxi Province, P. R. China;3. First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, P. R. China;4. The Second Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, P. R. China;5. Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, P. R. China
Abstract: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.
Keywords:apoptosis  calycosin  IκBα  miR-223  osteosarcoma
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