黄芪甲苷通过诱导细胞凋亡和调节 caspase 依赖性 Fas/FasL 信号通路对骨肉瘤细胞的化疗增敏作用。
Chemosensitive effects of Astragaloside IV in osteosarcoma cells via induction of apoptosis and regulation of caspase-dependent Fas/FasL signaling.
机构信息
Department of Orthopedics, Ningbo Fourth Hospital, Ningbo, Zhejiang, PR China.
Department of Radiotherapy and Chemotherapy, The 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
出版信息
Pharmacol Rep. 2017 Dec;69(6):1159-1164. doi: 10.1016/j.pharep.2017.07.001. Epub 2017 Jul 5.
BACKGROUND
The response of conventional chemotherapy for osteosarcoma treatment is usually poor, and chemotherapy-related severe side effects and drug resistance remain a problem. Abundant evidence has shown that Astragaloside IV, extracted from Astragalus membranaceus Bunge, strongly inhibits the growth of many carcinomas. We aimed to investigate the chemosensitive effects of Astragaloside IV in osteosarcoma in vitro and in vivo.
METHODS
Human osteosarcoma cell lines MG-63 and 143B, and BALB/c nu/nu mice xenograft were used. MTT, Clonogenic assay, Annexin V/PI assay and Western bloting analysis were carried out.
RESULTS
Our present study found that Astragaloside IV was a critical chemosensitizing agent for osteosarcoma treatment. Astragaloside IV suppressed cell proliferation and enhanced chemosensitivity in osteosarcoma cell lines and xenograft. Caspase-dependent Fas/FasL signaling was involved in cisplatin-induced apoptosis which was enhanced by Astragaloside IV.
CONCLUSION
It indicated that Astragaloside IV might be a promising therapeutic agent for osteosarcoma treatment.
背景
骨肉瘤治疗中常规化疗的反应通常较差，且与化疗相关的严重副作用和耐药性仍然是一个问题。大量证据表明，从黄芪中提取的黄芪甲苷 IV 强烈抑制多种癌的生长。我们旨在研究黄芪甲苷 IV 在骨肉瘤体内外的化疗增敏作用。
方法
使用人骨肉瘤细胞系 MG-63 和 143B 以及 BALB/c nu/nu 小鼠异种移植模型。进行 MTT、集落形成实验、Annexin V/PI 检测和 Western blot 分析。
结果
本研究发现黄芪甲苷 IV 是骨肉瘤治疗的关键化疗增敏剂。黄芪甲苷 IV 抑制骨肉瘤细胞系和异种移植中的细胞增殖并增强化疗敏感性。半胱天冬酶依赖性 Fas/FasL 信号参与顺铂诱导的凋亡，而黄芪甲苷 IV 增强了这种凋亡。
结论
表明黄芪甲苷 IV 可能是骨肉瘤治疗的一种有前途的治疗剂。
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