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学科主题: 药学
题名:
Methotrexate and 5-aminoimidazole-4-carboxamide riboside exert synergistic anticancer action against human breast cancer and hepatocellular carcinoma
作者: Cheng, Xiao-liang1,4; Zhou, Tian-yan1,2; Li, Bo3; Li, Meng-yao2; Li, Liang1,2; Li, Zai-quan3; Lu, Wei1,2
关键词: methotrexate ; 5-aminoimidazole-4-carboxamide riboside ; antitumor agents ; human breast cancer ; human hepatocellular carcinoma ; drug synergism ; pharmacokinetics ; AMP-activated protein kinase ; DNA synthesis
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2013-07-01
DOI: 10.1038/aps.2013.16
卷: 34, 期:7, 页:951-959
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: ACTIVATED PROTEIN-KINASE ; REDUCED FOLATE CARRIER ; LEUKEMIA-CELLS ; IN-VITRO ; APOPTOSIS ; ENERGY ; PATHWAY ; GROWTH ; PHARMACOKINETICS ; PROLIFERATION
英文摘要:

Aim: To investigate the influences of methotrexate (MTX) on the anticancer actions and pharmacokinetics of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) in human breast cancer and hepatocellular carcinoma.

Methods: Human breast cancer cell line MCF-7 and human hepatocellular carcinoma cell line HepG2 were examined. The cell proliferation was assessed using a sulforhodamine B assay. Western blotting and radioactivity assays were used to analyze the phosphorylation of AMPK. The DNA synthesis was analyzed with BrdU incorporation. Nude mice bearing MCF-7 cell xenografts were used to for in vivo study. MTX (50 mg/kg, ip, per week) and AICA riboside (200 mg/kg, ip, every other day) were administered the animals for 2 weeks. The concentrations of AICA riboside and its active metabolite AICA ribotide in the plasma and tumors were measured with HPLC.

Results: Synergistic cytotoxicity in vitro was observed with MTX (0.1, 0.5, and 1 mu mol/L) combined with AICA riboside (0.25-1 mmol/L) in MCF-7 cells, and with MTX (0.5 and 1 mu mol/L) combined with AICA riboside (0.5 and 1 mmol/L) in HepG2 cells. MTX (1 mu mol/L) significantly enhanced the AICA riboside-induced AMPK activation and BrdU incorporation in both MCF-7 and HepG2 cells. Co-treatment with MTX and AICA riboside exerted more potent inhibition on the tumor growth in nude mice than either drug alone. After injection of AICA riboside (200 mg/kg, iv) in nude mice bearing MCF-7 xenografts, MTX (50 mg/kg, iv) significantly increased the concentrations of AICA riboside and its active metabolite AICA ribotide in tumors.

Conclusion: MTX and AICA riboside exert synergistic anticancer action against MCF-7 and HepG2 cells in vitro and in vivo. MTX increases the concentration of AICA riboside and its active metabolite AICA ribotide in tumors in vivo.

语种: 英语
所属项目编号: BMU20110263E
项目资助者: Innovation Team of Ministry of Education, China
WOS记录号: WOS:000321332700011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52436
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
4.Xi An Jiao Tong Univ, Coll Med, Affiliated Hosp 1, Dept Pharm, Xian 710061, Peoples R China

Recommended Citation:
Cheng, Xiao-liang,Zhou, Tian-yan,Li, Bo,et al. Methotrexate and 5-aminoimidazole-4-carboxamide riboside exert synergistic anticancer action against human breast cancer and hepatocellular carcinoma[J]. ACTA PHARMACOLOGICA SINICA,2013,34(7):951-959.
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