多西紫杉醇-聚乙二醇-聚己内酯嵌段共聚物胶束治疗裸鼠前列腺癌的研究  

Anti-cancer effect of DTX-PEG-PCL block copolymer micelles on prostate cancer xenograft nude mice models

作　　者：朴圣君 李晓刚[1] 吴文元[1] 阿卜杜拉-阿利 金铁雄[1] 杨为民[3] 高钟镐[4] 

机构地区：[1]延边大学附属延边医院泌尿外科,吉林延吉133000 [2]阿富汗Balkh医学院泌尿外科 [3]华中科技大学同济医学院附属同济医院泌尿外科 [4]中国医学科学院药物研究所

出　　处：《临床泌尿外科杂志》2014年第8期721-725,共5页Journal of Clinical Urology

基　　金：吉林省科技厅自然科学基金项目(编号201215231)

摘　　要：目的:探讨多西紫杉醇-聚乙二醇-聚己内酯嵌段共聚物(DTX-PEG-PCL)胶束治疗裸鼠前列腺癌的作用。方法:体外培养人前列腺癌LNCaP-C4-2B细胞,并皮下接种30只裸鼠构建前列腺癌裸鼠模型。随机分为3组(10只/组):模型组、DTX组(阳性组)及DTX-PEG-PCL组(胶束组)。尾静脉注射给药20mg/kg,每3天1次,共3次。模型组给予生理盐水,阳性组注射市售的多西紫杉醇注射液,胶束组注射自制的DTX-PEG-PCL胶束溶液。计算各组肿瘤体积,绘制肿瘤生长曲线,测定PSA值,组织病理学和免疫组化方法评价药物对移植瘤的抑制作用。结果:1肿瘤体积:阳性组、胶束组的肿瘤体积均下降,但模型组的肿瘤体积上升,阳性组、胶束组分别与模型组进行比较,组间差异均有统计学意义(P<0.05),但胶束组与阳性组进行比较,差异无统计学意义(P>0.05);2血清PSA值:与模型组、阳性组相比,胶束组血清PSA值下降更加明显,差异有统计学意义(P<0.05);3组织病理学检测:胶束组与阳性组比较,该组癌细胞核分裂象减少未见癌栓形成,肿瘤细胞团中广泛纤维组织增生,分割成团块状,可见大灶性癌细胞水肿,变性,坏死;4免疫组化检测:VEGF、COX-2、bcl-2在肿瘤组织当中的阳性表达比较,阳性组、胶束组的表达与模型组相比明显减低,而且胶束组与阳性组相比,表达强度更为减低。结论:本研究标明,DTX-PEG-PCL与市售的多西紫杉醇相比是一种治疗激素非依赖性前列腺癌的有更好疗效和广阔应用前景的药物。Objective：To investigate anti-cancer effect of DTX-PEG-PCL block copolymer micelles on prostate cancer xenograft nude mice models.Method：Human prostate cancer cells LNCaP-C4-2Bwere cultured in vitro and inoculated subcutaneously in 30 nude mice models which were randomly divided into three groups（10 mice/group）.The data of three groups were as follows：control group were treated by normal saline;DTX group were treated by docetaxel dissolved in PBS;DTX-PEG-PCL group were treated by DTX-PEG-PCL micelles.All mice models were injected intravenously via the tails vein at a dose of 20mg/kg once a day every two days for three times.After the treatment we calculated the tumor volume,mapped the growth curve,measured PSA level and done HE staining and immunohistochemical analysis to evaluate the drug suppression of tumor.Result：1The tumor volumes in DTX-PEG-PCL group and DTX group were smaller than control group which was statistically significant（P〈0.05）,while there was no significant difference（P〉0.05）between DTX-PEG-PCL group and DTX group.2According to results of PSA,DTX-PEG-PCL group had lower level of PSA than other two groups,which was a statistically significant difference（P〈0.05）.3 HE staining indicated that DTX-PEG-PCL group had low mitotic cells,no tumor thrombus,and extensive fibrous tissues were developed among cancer mass and divided into two separated mass.Also we could see significant focal degeneration and necrosis of cancer cells.4Immunohistochemistry results indicated that the positive rate levels of VEGF,COX-2,Bcl-2in DTX-PEG-PCL micelle group were lower than DTX group or control group.Conclusion：DTX-PEG-PCL micelles are worth using generously for they have better effects than docetaxel on hormone refractory prostate cancer.

关 键 词：前列腺癌 LNCaP-C4-2B细胞 多西紫杉醇 共聚物胶束 

分 类 号：R737.25[医药卫生—肿瘤]