基于胰腺癌患者来源异种移植模型的化疗药物筛选  

Chemoterapeutic drug screening based on patient-derived pancreatic cancer xenograft(PDX) models

作　　者：张贺 陈薛[1] 张彩勤 赵勇[1] 谭邓旭[1] 师长宏 ZHANG He;CHEN Xue;ZHANG Caiqin;ZHAO Yong;TAN Dengxu;SHI Changhong(Laboratory Animal Center, the Fourth Military Medical University, Xi＇ an 710032,China;Department of Medical Administration, the Genernal Hospital of Shenyang Military Region, Shenyang 110015)

机构地区：[1]第四军医大学实验动物中心,西安710032 [2]原沈阳军区总医院医务部,沈阳110015

出　　处：《中国实验动物学报》2018年第1期29-35,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(No.31572340,No.31772546); 军队实验动物专项课题(No.SYDW2016-006)

摘　　要：目的利用胰腺癌PDX模型,评估临床化疗药物治疗效果,筛选个体化治疗方案。方法将新鲜的胰腺癌手术标本移植裸鼠皮下,建立PDX模型并稳定传代;利用STR基因分型检测PDX模型肿瘤组织的溯源性;选择临床使用的奥沙利铂、吉西他滨和伊立替康三种化疗药物进行治疗,并测量肿瘤体积;利用TGD值数学模型方法,辅以血浆CA19-9检测评估三种化疗药物的治疗效果。结果 PDX模型肿瘤组织样本的溯源性为99.99%,与原发瘤保持一致;与对照组相比,伊立替康组和吉西他滨组均具有显著的治疗效果(P=0.001),且吉西他滨抑瘤效果更为明显;伊立替康的药物毒性作用最小,吉西他滨次之。结论成功建立胰腺癌PDX模型并稳定传代,通过TGD值数学模型法筛选,发现吉西他滨抑制肿瘤生长效果最为显著,推荐其作为该胰腺癌个体化治疗首选药物。Objective To evaluate the therapeutic effect of chemotherapeutic drugs on pancreatic carcinoma based on patient-derived xenograft（ PDX） models,and to screen an individualized treatment strategy. Methods Fresh human pancreatic carcinoma tissues were subcutaneously transplanted into nude mice to establish PDX models which could be stably passaged. The traceability of PDX models was determined by STR analysis. The PDX models were treated with three different clinical chemotherapeutic drugs oxaliplatin,gemcitabine and irinotecan,respectively,and the tumor volumes were measured at different times. The therapeutic effect of those drugs was assessed by TGD mathematical model and plasma CA19-9 test. Results The traceability of patient-derived xenograft samples was up to 99. 99%. Compared with the control group,the treatment with irinotecan and gemcitabine inhibited tumor growth significantly（ P = 0. 001）,and gemcitabine had even better result. The minimum toxic effect in the mice was induced by irinotecan treatment,followed by gemcitabine treatment. Conclusions Pancreatic carcinoma PDX models are successfully established and can be stably passaged. Gemcitabine shows the most inhibitory effect on tumor growth based on TGD mathematical model assessment,and deserves to be recommended as the preferred drug for individual treatment of pancreatic carcinoma.

关 键 词：胰腺癌 PDX模型 个体化治疗 药物筛选 TGD值数学模型 

分 类 号：Q95-33[生物学—动物学]