学科主题临床医学
Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis
Zhao, Hui; Guo, Wei; Peng, Changliang; Ji, Tao; Lu, Xinchang
关键词Arsenic trioxide Osteosarcoma Apoptosis MDR
刊名MOLECULAR BIOLOGY REPORTS
2010-06-01
DOI10.1007/s11033-009-9765-2
37期:5页:2509-2515
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]ACUTE PROMYELOCYTIC LEUKEMIA ; HIGH-DOSE METHOTREXATE ; OSTEOGENIC-SARCOMA ; PREOPERATIVE CHEMOTHERAPY ; MULTIDRUG-RESISTANCE ; P-GLYCOPROTEIN ; CROSS-RESISTANCE ; EXPERIENCE ; GLUTATHIONE ; ACTIVATION
英文摘要

Given that arsenic trioxide (As(2)O(3)) has been successfully used as a chemotherapeutic agent for refractory malignant tumors, this study is aimed at investigating the effect of As(2)O(3) on human Adriamycin resistant osteosarcoma cell line Saos-2. The mechanism underlying multi drug resistance (MDR) in osteosarcoma cells and the anti-tumor effect of As(2)O(3) on Adriamycin resistant osteosarcoma cells were analyzed. In our experiment, we first selected Adriamycin resistant osteosarcoma cell line by growing the classic osteosarcoma cell line Saos-2 in the medium with increasing drug concentrations. Then, we compared the IC50s of the osteosarcoma cells treated with different anticancer drugs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Subsequently, we assessed the expression of classic MDR related molecules, Pgp, multidrug resistance-associated protein (MRP) and glutathione (GSH) activity in the wild type and Adriamycin resistant Saos-2 cells. Furthermore, the apoptosis was assessed by concerning DNA fragment and flow cytometry with Annexin-V staining. To elucidate the underlying mechanism of the apoptosis, related proteins Bcl-2, Bcl-xL, Bax, Bak, cleaved Caspase-3 and cleaved Caspase-9 were analyzed by western blotting. The data showed that the resistance to Adriamycin affected the sensitivity of osteosarcoma cell to other chemotherapeutic agents. The IC50s of Saos-2/ADM cells for methotrexate (1.74-fold), Cisplatin (1.43-fold) and As(2)O(3) (1.21-fold) were increased compared with Saos-2 control cells. The expression of Pgp was upregulated comparing with the control cells. No significant difference was detected about the MRP and the glutathione-S-transferase activity and intracellular GSH concentration among different treated osteosarcoma cells. Apoptosis was observed and proved. The western blotting showed that the expression of Bcl-2 and Bcl-xL was downregulated. Meanwhile, the level of Bax, Bak, cleaved Caspase-3 and cleaved Caspase-9 was upregulated after treated with As(2)O(3). The study suggests that Adriamycin resistant osteosarcoma cells have good response to As(2)O(3)-based chemotherapy in vitro, probably via the pathway of inducing apoptosis. And As(2)O(3) might serve as an excellent alternative candidate for adjuvant chemotherapeutic agent on this incurable pediatric sarcoma.

语种英语
WOS记录号WOS:000279308400048
项目编号2005-1009
资助机构Capital Development Foundation of Beijing
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58648
专题北京大学药学院_天然药物与仿生药物国家重点实验室
北京大学第二临床医学院_骨肿瘤科
作者单位Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing 100044, Peoples R China
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GB/T 7714
Zhao, Hui,Guo, Wei,Peng, Changliang,et al. Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis[J]. MOLECULAR BIOLOGY REPORTS,2010,37(5):2509-2515.
APA Zhao, Hui,Guo, Wei,Peng, Changliang,Ji, Tao,&Lu, Xinchang.(2010).Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis.MOLECULAR BIOLOGY REPORTS,37(5),2509-2515.
MLA Zhao, Hui,et al."Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis".MOLECULAR BIOLOGY REPORTS 37.5(2010):2509-2515.
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