A nucleoside analog with anticancer activity
Ethynylcitidine (ECyD) is a nucleoside analog with anticancer activity.1,2 It is cytotoxic to A549, NUGC-3, HT-29, MIA PaCa-2, and MCF-7 cancer cells (IC50s = 0.114, 1.032, 0.539, 0.198, and 0.326 ?M, respectively).1 ECyD (0.25 mg/kg per day) reduces tumor growth in CADO-LC11 lung, PAN-12 pancreas, AZ-521 stomach, and CO-3 colon cancer mouse xenograft models.2
1.Shimamoto, Y., Fujioka, A., Kazuno, H., et al.Antitumor activity and pharmacokinetics of TAS-106, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosineJpn. J. Cancer Res.92(3)343-351(2001) 2.Takatori, S., Kanda, H., Takenaka, K., et al.Antitumor mechanisms and metabolism of the novel antitumor nucleoside analogues, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine and 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)uracilCancer Chemother. Pharmacol.44(2)97-104(1999)
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Cell experiment: |
MIAPaCa-2 cells are maintained in Dulbecco’s modified Eagle’s medium supplemented with 10% FCS and 2.5% horse serum. Cells in the exponential growth phase are seeded onto 6-well plates (5×104 cells/1.8 mL/well) on day 0. Twenty-four hours after seeding, on day 1, Ethynylcytidine (TAS-106) (6 concentrations range from 0 to 100 μM) is added to cultured cells (3 wells at each concentration) at a volume of 0.2 mL/well. After 4 and 24 h, on the 4 and 24 h Ethynylcytidine exposure schedules, the drug-containing medium is removed, and the cells are washed twice with Dulbecco’s phosphate buffered saline and subsequently cultured in drug-free medium until day 4. On the 72 h exposure schedule, after adding the Ethynylcytidine, cells are cultured continuously until day 4. On day 4, cell numbers are determined and converted to values related to the cell numbers on day 1. The concentration of Ethynylcytidine which inhibits cell growth by 50% (IC50) is calculated from this relative cell growth. Two or three individual experiments are conducted on each cell line to confirm reproducibility[1]. |
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Animal experiment: |
Nude rats s.c. transplanted with LX-1 human lung tumors are given a single i.v. dose of [3H]Ethynylcytidine (TAS-106) (6 mg/kg, 3.7 MBq/kg). For analysis of the distribution of radioactivity and intratumoral Ethynylcytidine metabolism, serum and various tissues (tumor, skin, lung, liver, kidney, spleen, small intestine, large intestine, testis, brain, and bone marrow cells) are sampled from 3 rats at each of the following 6 time points: 0.5, 1, 2, 4, 8 and 24 h after i.v. administration. At each point in time, bone marrow cells are collected from the 3 rats and combined into a cell pellet. All samples of serum, bone marrow cell pellets, and tissues are immediately frozen on dry ice and stored at -30°C until used[1]. |
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参考文献: [1]. Shimamoto Y, et al. Antitumor activity and pharmacokinetics of TAS-106, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine. Jpn J Cancer Res. 2001 Mar;92(3):343-51. |
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