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IR@PKUHSC  > 北京大学第二临床医学院  > 骨肿瘤科  > 期刊论文
学科主题: 临床医学
题名:
Arsenic trioxide inhibits the growth of Adriamycin resistant osteosarcoma cells through inducing apoptosis
作者: Zhao, Hui; Guo, Wei; Peng, Changliang; Ji, Tao; Lu, Xinchang
关键词: Arsenic trioxide ; Osteosarcoma ; Apoptosis ; MDR
刊名: MOLECULAR BIOLOGY REPORTS
发表日期: 2010-06-01
DOI: 10.1007/s11033-009-9765-2
卷: 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
所属项目编号: 2005-1009
项目资助者: Capital Development Foundation of Beijing
WOS记录号: WOS:000279308400048
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58648
Appears in Collections:北京大学第二临床医学院_骨肿瘤科_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing 100044, Peoples R China

Recommended Citation:
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.
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