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目的通过用DDC(Diethyldithiocarbamate)预先处理耐药肿瘤细胞和荷有Walk 2 5 6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 2 2 0 - 2 5 0gSD大鼠建立Walk 2 5 6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SGC790 1 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 0 1)。而生命延长率则明显小于预先用DDC处理过的各组 (P <0 0 5 )。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。
OBJECTIVE: To investigate the feasibility of using this method to improve the anti-tumor effects of nanoscale doxorubicin lipiodol emulsion in vitro and in vivo by using DDC (Diethyldithiocarbamate) to pre-treat drug-resistant tumor cells and rats with Walk 2 56 liver cancer model. Methods MTT assay was used to evaluate the killing effect of doxorubicin and its nanoscale lipiodol emulsion on drug-resistant cells and tumor cells. The model of Walk 2 5 6 hepatocellular carcinoma was established with 220-250 g SD rats and injected with hepatic artery Saline, doxorubicin, nano-doxorubicin lipiodol emulsion. DDC plus nanoscale doxorubicin lipiodol emulsion and DDC plus doxorubicin liposome lipiodol emulsion were measured in each group of tumor growth rate and life extension rate. Results After pretreatment with DDC, the IC50 (μg mL-1) of doxorubicin in two doxorubicin-resistant tumor cells SGC790 1 CVR and SGC790 WT decreased from 0 4 74 to 0 74 and from 4 0 to 0 32. In addition to saline, the volume of tumor after treatment decreased, but the average tumor growth rate of each group without DDC treatment was far greater than that of DDC group (P <0.01). While the rate of prolongation of life was significantly less than that of DDC group (P <0.05). Conclusion Pretreatment with DDC to inhibit SOD in tumor cells can enhance the antitumor effect of doxorubicin. Liposomes and n-butyl polycyanoacrylate nanoparticles were used as the carrier for the release of doxorubicin, Relieved and certain tissue targeting, delayed the tumor cells by DDC inhibition of superoxide, enhance the role of free radicals in tumor cells and improve the curative effect.