用DDC预处理肝癌提高阿霉素纳米粒的抗肿瘤效果

用DDC预处理肝癌提高阿霉素纳米粒的抗肿瘤效果

吴道澄^*, 万明习, 莫简

1.西安交通大学生物医学工程系, 西安 710038;
2.第四军医大学药物化学教研室, 西安 710032

收稿日期:2002-03-20 修回日期:2002-06-15 出版日期:2002-09-15 发布日期:2002-09-15
通讯作者: 吴道澄*

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

Wu Daocheng^*, Wan Mingxi, Mo Jian

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*

摘要/Abstract

摘要： 目的通过用DDC(Diethyldithiocarbamate)预先处理耐药肿瘤细胞和荷有Walk-256肝癌模型的大鼠的方法, 考察此方法对提高纳米级阿霉素碘油乳剂体内外抗肿瘤作用的可行性. 方法用MTT试验评价阿霉素及其纳米级碘油乳剂对耐药细胞及肿瘤细胞的杀灭作用, 用220-250g SD大鼠建立Walk-256肝癌模型, 通过肝动脉分别注入生理盐水、阿霉素、纳米级阿霉素碘油乳剂.DDC加纳米级阿霉素碘油乳剂以及DDC加阿霉素脂质体碘油乳剂, 分别测定各组的肿瘤生长率和生命延长率. 结果经过DDC预处理后,阿霉素对两种阿霉素耐药肿瘤细胞SGC7901/CVR和SGC790/WT的IC50(μg.mL^-1)分别从原来的18.4降至0.74和从4.0降至0.32.除生理盐水外, 各组处理后的肿瘤体积均有所下降, 未用DDC处理过各组的平均肿瘤生长率远大于预先用DDC处理过的各组(P<0.01). 而生命延长率则明显小于预先用DDC处理过的各组(P<0.05). 结论通过用DDC预先处理来抑制肿瘤细胞中的SOD可以提高阿霉素的抗肿瘤作用, 脂质体和聚氰基丙烯酸正丁酯纳米粒作为阿霉素的释放载体, 使阿霉素具有缓释性和一定的组织靶向性, 延缓了肿瘤细胞中被DDC抑制的超氧化物, 增强肿瘤细胞中自由基的作用, 提高了疗效.

关键词: Vilsmeier反应, N,N-二甲氨基甲基苯亚胺, 合成

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

Supporting: ^*Correspondence author present address: Department of Pharmaceutical Chemistry , The Fourth Military Medical Unviersity, Xi’an 710032. P.R.China.
Tel: +86-29-3373849. Fax: +86-29-3373849. E-mail: cnxxl@yahoo.com

吴道澄^*, 万明习, 莫简. 用DDC预处理肝癌提高阿霉素纳米粒的抗肿瘤效果[J]. .

Wu Daocheng^*, Wan Mingxi, Mo Jian . Enhancing the Antitumor Effect of Adriamycin Nanoparticles by Pretreating Liver Cancer with Diethyldithiocarbamate[J]. .

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