胰高血糖素样多肽-1诱导吉非替尼筛选富集的胰腺癌干细胞分化  

GLP-1-induced diferentiation of pancreatic cancer stem cells screened by geitinib

作　　者：丁雯[1,2] 李金龙[1,2] 徐岚[1] 惠宏襄[1,2,3] 

机构地区：[1]南方医科大学生物技术学院生物治疗研究所国际代谢病中心,广东广州510518 [2]东莞南方医大代谢医学研发有限公司研发中心,广东东莞523000 [3]美国加州大学洛杉矶医学院胰腺病中心,洛杉矶90095

出　　处：《肿瘤》2014年第5期413-418,共6页Tumor

摘　　要：目的 :通过化疗药物筛选富集胰腺癌干细胞,观察胰高血糖素样多肽-1(glucagon-like peptide-1,GLP-1)诱导胰腺癌干细胞的分化。方法 :应用0.05 mmol/L吉非替尼连续培养胰腺癌Panc-1细胞2周,筛选出吉非替尼耐药的S-Panc-1(selected Panc-1)细胞,并用10 nmol/L GLP-1处理72 h(命名为G-S-Panc-1细胞)。分别应用FCM法检测Panc-1、S-Panc-1和G-S-Panc-1细胞中CD133+细胞所占的比例,软琼脂克隆形成实验检测Panc-1和S-Panc-1细胞的克隆形成能力,裸鼠移植瘤实验检测S-Panc-1和G-S-Panc-1细胞的体内成瘤能力。结果 :S-Panc-1细胞中CD133+细胞所占比例[(55.5±1.7)%]明显高于Panc-1细胞[(1.7±0.2)%](P<0.01),G-S-Panc-1细胞中CD133+细胞所占比例明显下降(P<0.01),S-Panc-1细胞的体外克隆形成率[(1.20±0.16)%]明显高于Panc-1细胞[(0.31±0.02)%](P<0.01),G-S-Panc-1细胞裸鼠体内的成瘤能力明显低于S-Panc-1细胞(P<0.01)。结论 :吉非替尼耐药的Panc-1细胞具有肿瘤干细胞特征,GLP-1对胰腺癌干细胞可能具有诱导分化的作用。Objective： To enrich pancreatic cancer stem cells by screening using chemotherapeutic drug and observe glucagon-like peptide-1 （GLP-1）-induced differentiation of pancreatic cancer stem cells. Methods： Panc-1 cells were treated with 0.05 mmol/L gefinitib for two weeks to screen out gefinitib- resistant cells [named as selected Panc-1 （S-Panc-1） cells]. Then the S-Panc-1 cells were treated with 10 nmol/L GLP-1 for 72 h （named as G-S-Panc-1 cells）. The percentages of CD133＋ in Panc-1, S-Panc-1 and G-S-Panc-1 cells were detected by flow cytometry. The abilities of colony formation of Panc-1 and S-Panc-1 cells were determined by soft agar colony formation assay. The abilities of tumor formation of S-Panc-1 and G-S-Panc-1 cells in nude mice were examined by xenograft tumor. Results： The percentage of CD133＋ in S-Panc-1 cells [（55.5±1.7）%] was higher than that in Panc-1 cells [（1.7±0.2）%] （P 〈 0.01）. The percentage of CD133＋ in G-S-Panc-1 cells was significantly reduced （P 〈 0.01）. The ratio of colony formation of S-Panc-1 cells [（1.20±0.1 6）%] was higher than that of Panc-1 cells [（0.31 ±0.02）%] （P 〈 0.01）. The ability of tumor formation of G-S-Panc-1 cells was lower than that of S-Panc-1 cells in nude mice （P 〈 0.01）. Conclusion： Gefinitib-resistant Panc-1 cells display the characteristics of cancer stem cells. GLP-1 may induce the differentiation of pancreatic cancer stem cells.

关 键 词：胰腺肿瘤 肿瘤干细胞 细胞分化 吉非替尼 GLP-1 

分 类 号：R735.9[医药卫生—肿瘤]