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毛蕊异黄酮通过诱导凋亡对骨肉瘤的抗肿瘤作用:体外和体内研究

Antineoplastic effect of calycosin on osteosarcoma through inducing apoptosis showing in vitro and in vivo investigations.

作者信息

Qiu Rubiao, Ma Gang, Zheng Chenguang, Qiu Xiaoxia, Li Xinning, Li Xueyu, Mo Jianlan, Li Zhengzhao, Liu Yun, Mo Linjian, Bi Guan, Ye Yu

机构信息

Guangxi Maternal and Child Health Hospital, Nanning, Guangxi Zhuang Autonomous Region 530003, PR China.

Emergency Department, Western Hospital, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, PR China.

出版信息

Exp Mol Pathol. 2014 Aug;97(1):17-22. doi: 10.1016/j.yexmp.2014.04.014. Epub 2014 May 4.

Abstract

Recently, increasing studies have documented that tumorigenesis closely relates to apoptotic processes. Thus, inducing apoptosis is an anti-cancer strategy against osteosarcoma. Here we investigated the anti-proliferative effect of calycosin on human osteosarcoma cell (143B) in vitro. The results showed that calycosin dose-dependently inhibited 143B cell proliferation as reflected in tetrazolium salt (MTT) assay (P<0.01). In addition, calycosin effectively down-regulated cellular mRNA expressions of IκBα, NF-κB p65 and cyclin D1 through RT-PCR assay (P<0.01). Next, calycosin-mediated inhibitory effect on 143B tumor-bearing nude mice and the underlying mechanism were evaluated and discussed. As a result, calycosin administration significantly blocked solid tumor growth in 143B-harbored nude mice (P<0.01). Furthermore, intracellular Bcl-2 protein expression was effectively reduced in 143B-harbored tumor tissue through western blotting analysis (P<0.01), while intratumoral Apaf-1 and cleaved Caspase-3 protein levels were up-regulated, respectively (P<0.01). Taken together, calycosin possesses the anti-osteosarcoma potential, in which the mechanism involved was associated with activation of apoptotic, thus inducing apoptosis.

摘要

最近,越来越多的研究表明肿瘤发生与凋亡过程密切相关。因此,诱导凋亡是一种针对骨肉瘤的抗癌策略。在此,我们研究了毛蕊异黄酮对人骨肉瘤细胞(143B)的体外抗增殖作用。结果显示,四唑盐(MTT)检测表明毛蕊异黄酮剂量依赖性地抑制143B细胞增殖(P<0.01)。此外,通过逆转录聚合酶链反应(RT-PCR)检测发现,毛蕊异黄酮有效下调细胞中IκBα、NF-κB p65和细胞周期蛋白D1的mRNA表达(P<0.01)。接下来,评估并讨论了毛蕊异黄酮对荷143B瘤裸鼠的抑制作用及其潜在机制。结果表明,给予毛蕊异黄酮可显著抑制荷143B瘤裸鼠实体瘤的生长(P<0.01)。此外,通过蛋白质免疫印迹分析发现,荷143B瘤组织中细胞内Bcl-2蛋白表达有效降低(P<0.01),而肿瘤组织内Apaf-1和裂解的Caspase-3蛋白水平分别上调(P<0.01)。综上所述,毛蕊异黄酮具有抗骨肉瘤的潜力,其作用机制与激活凋亡相关,从而诱导细胞凋亡。

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