吉西他滨缓释微球间质化疗治疗胰腺癌的实验研究  

Effect of interstitial chemotherapy of PLGA-gemcitabine microsphere on pancreatic cancer

作　　者：李井泉[1] 赵平[1] 王世亮[2] 王铮[1] 李爱东[1] 张永明[1] 韩志楷[1] 马洁[1] 

机构地区：[1]中国医学科学院 北京协和医学院 肿瘤医院肿瘤研究所,北京100021 [2]合肥工业大学控释药物研究室,合肥230009

出　　处：《癌症进展》2008年第6期601-606,共6页Oncology Progress

摘　　要：目的研究(聚乳酸-乙醇酸共聚物)PLGA-吉西他滨(GEM)缓释微球间质化疗应用于胰腺癌的治疗效果。方法将80只胰腺癌荷瘤鼠随机分为8组,每组10只。A1、A2、A3组瘤内注射PLGA-GEM缓释微球,给药剂量分别为5mg/kg、2.5mg/ kg和1.25mg/kg;B组瘤内注射GEM(5mg/kg)对照;C组腹腔内注射GEM 5mg/kg;D组瘤内注射PLGA-5-Fu缓释微球5mg/kg;E组为PLGA载体5mg/kg对照;F组不接受任何治疗。于给药前、给药后4、8、12、16、20、24天观察裸鼠生存状况、称体重、测量肿瘤大小,绘制肿瘤生长曲线;24天时处死动物,称瘤重,计算抑瘤率;行免疫组化染色,了解VEGF表达情况。结果PLGA-GEM缓释微球瘤内给药高、中剂量组(A1、A2组)抑瘤率分别达到了66%和40%,与其他组相比结果具有统计学差异(P<0.05);随着PLGA-GEM缓释微球剂量的增加,VEGF表达降低,A1、A2组与F组相比,结果具有统计学差异(P<0.05)。各组体重在治疗后各观察点与治疗前比较,没有统计学差异。结论PLGA-GEM缓释微球能有效抑制胰腺癌移植瘤的VEGF表达,能显著抑制肿瘤的生长,且无明显的毒副作用,该制剂具有一定的潜在临床应用价值。Objective To study the antitumor effect of slow-release PLGA （ polylactic-co-glycolic acid） - gemcitabine microsphere on xenograft pancreatic tumor in mice. Methods Totally 80 tumor - bearing nude mice were randomly divided into eight groups for different treatments. Group A1, A2, and A3 were treated with intratumoral injection of PLGA-gemcitabine microsphere, and the doses of gemcitabine were 5mg/ kg, 2. 5mg/kg, and 1.25mg/kg, respectively. Group B was treated with intratumoral gemcitabine injection, and the dose was 5 mg/kg. Group C was treated with abdominal cavity injection of gemcitabine, and the dose was 5 mg/kg. Group D was treated with intratumoral injection of PLGA-5-Fu microsphere, and the dose of 5 -Fu was 5mg/kg. Group E was treated with intratumoral injection of PLGA, and the dose was 5 mg/kg; Group F did not receive any treatment. On the days of 0 and 4, 8, 12, 16, 20, 24 after the drug injection, health condition and body mass was weighed, the size of the tumor were observed, and the growth curve was drawn. At the end of the experiment, the weight of the tumor was measured and tumor inhibiting rate was calculated, and the tumor expression of VEGF was measured in group A1, A2, A3 and F. Results Tumor inhibiting rate of group A1 and A2 were 66% and 40% respectively, and there were statistical differences between groups A1, A2 and other groups （P 〈 0. 05 ）. Expression of VEGF decreased follow the dose increase of PLGA - Gemcitabine microsphere, there were statistical differences between A1, A2 and F groups （ P 〈 0. 05 ）. The weight changed before and after treatment in every group had no statistical differences. Conclusion Interstitial chemotherapy of PLGA- gemcitabine microsphere can effectively reduce the expression of VEGF and restrain the tumor growth. PL- GA-gemcitabine microsphere has no evident side effects and is clinically beneficial.

关 键 词：裸鼠 胰腺癌 吉西他滨 微球间质化疗 

分 类 号：R73-761[医药卫生—肿瘤] R735.9[医药卫生—临床医学]