We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Methotrexate and 5-aminoimidazole-4-carboxamide riboside exert synergistic anticancer action against human breast cancer and hepatocellular carcinoma.
- Authors
Cheng, Xiao-liang; Zhou, Tian-yan; Li, Bo; Li, Meng-yao; Li, Liang; Li, Zai-quan; Lu, Wei
- Abstract
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 μmol/L) combined with AICA riboside (0.25-1 mmol/L) in MCF-7 cells, and with MTX (0.5 and 1 μmol/L) combined with AICA riboside (0.5 and 1 mmol/L) in HepG2 cells. MTX (1 μmol/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.
- Subjects
METHOTREXATE; IMIDAZOLES; CARBOXAMIDES; RIBOSIDES; ANTINEOPLASTIC agents; BREAST cancer; LIVER cancer
- Publication
Acta Pharmacologica Sinica, 2013, Vol 34, Issue 7, p951
- ISSN
1671-4083
- Publication type
Article
- DOI
10.1038/aps.2013.16