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Enhanced antitumor effect of TM208 in combination with 5-fluorouracil in H22 transplanted mice

Lin Jia, Bo Xu, Wei Guo, Ze-Mei Ge, Run-Tao Li, Jing-Rong Cui*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
    2. Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2011-03-30 Revised:2011-08-30 Online:2011-11-15 Published:2011-11-15
  • Contact: Jing-Rong Cui*

Abstract:

4-Methylpiperazine-1-carbodithioc-acid-3-cyano-3,3-diphenylpropyl ester hydrochloride (TM208), a newly synthesized dithiocarbamate derivative, exhibits antitumor effect in vivo with low toxicity. However, the antitumor effect of TM208 in combination with drugs in clinical use for cytotoxic chemotherapy has not been identified. In our study, the antitumor effects and toxicities of TM208 in combination with cisplatin (DDP), cyclophosphamide (CTX) and 5-fluorouracil (5-Fu), respectively, were evaluated in vivo using a transplanted solid-type hepatocarcinoma H22 mice model. The results suggested that 5-Fu (5 mg/kg/2d) potentiated the antitumor effect of TM208 (100 mg/kg/d) with significantly higher tumor inhibition rates (P<0.01) and a slight elevation of toxicity; however, DDP and CTX in combination with TM208 did not exhibit