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Enhancing the Antitumor Effect of Adriamycin Nanoparticles by Pretreating Liver Cancer with Diethyldithiocarbamate

Wu Daocheng*, Wan Mingxi, Mo Jian   

  1. 1.Department of Biomedical Engineering, Xi'an Jiaotong University, Xi'an 710038;
    2.Department of Pharmaceutical Chemistry, The Fourth Military Medical University, Xi'an 710032
  • Received:2002-03-20 Revised:2002-06-15 Online:2002-09-15 Published:2002-09-15
  • Contact: Wu Daocheng*

Abstract: Objective To examine the possibility of enhancing adriamycin nanoparticles antitumor effect by pretreating the tumor cells with diethyldithiocarbamate(DDC). Methods The cytotoxicity of adriamycin in cells was evaluated using MTT assay. Walk-256 carcinoma was transplanted to the livers of SD rats. Seven days later, the rats were divided into five groups, which were treated, respectively, by delivering saline(control), adriamycin, adriamycin nanoparticle lipiodol, a suspension containing DDC and adriamycin nanoparticle-lipiodol emulsion, a suspension containing DDC and adriamycin liposome lipiodol emulsion to the livers bearing carcinoma by injection through gastroduodenal artery. The distribution of adriamycin in rat tissues after administration was measured by HPLC. Results The value of the IC50 (μg·mL-1) of ADM was reduced from 18-4 to 0-74 for the resistant cells SGC7901/CVR, and from 4.0 to 0.32 for the sensitive cells SGC7901/WT by pretreating the tumor cells with DDC. The volume of every tumor in the rats treated with both DDC and adriamycin nanoparticle- lipiodol or DDC and adriamycin liposome-lipiodol emulsion decreased after the treatment. The volume of every tumor in the rats treated only with ADM or adriamycin nanoparticle lipiodol still increased. The mean values of tumor growth rate(G%) in rats decreased greatly in groups pretreated by DDC than in adriamycin nanoparticle-lipiodol or adriamycin liposome-lipiodol emulsion groups. The life prolongation rate (LPR%) in the rats treated with both DDC and adriamycin nanoparticle-lipiodol or DDC and adriamycin liposome-lipiodol emulsion increased significantly than in the rats treated only with adriamycin or adriamycin nanoparticle-lipiodol. Conclusion The antitumor effect of adriamycin can be enhanced by inhibiting the SOD in tumor cells with DDC.

Key words: Tumor, Tumor, Adriamycin, Adriamycin, Diethyldithiocarbamate, Diethyldithiocarbamate, Superoxide, Superoxide, Nanoparticle, Nanoparticle, Injection, Injection

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