奥曲肽对多烯紫杉醇耐药肿瘤细胞DU145的增敏作用及机制  

Synergism and Mechanism of Octreotide on Docetaxel-resistant Cancer Cell DU145

作　　者：甄明慧 冯国清[2] 杜英[1] 李付光 龚光明[1] 张博 朱沙[1] 

机构地区：[1]郑州大学基础医学院微生物学与免疫学教研室,郑州450001 [2]郑州大学基础医学院机能实验中心,郑州450001

出　　处：《肿瘤防治研究》2014年第6期562-567,共6页Cancer Research on Prevention and Treatment

摘　　要：目的研究奥曲肽(Octreotide,OCT)对多烯紫杉醇(Docetaxel,DTX)耐药前列腺癌细胞DU145药物敏感度的影响及可能机制。方法 MTT法检测DTX﹑OCT及OCT(100 nM)与各浓度DTX联合应用对DU145细胞的抑制作用,后续实验分四组:对照组﹑OCT组﹑DTX/OCT组及DTX组;RT-PCR检测各组VEGFA﹑Caspase9﹑Caspase 3及ATP-binding cassette,sub-family B(MDR/TAP),member 1(ABCB1)的表达;划痕实验检测各组细胞迁移能力。结果 DTX/OCT联合用药抑制率为(55.70±0.08)%,高于单独用药组DTX组(26.23±0.03)%和OCT组(24.77±0.04)%,P均﹤0.01。OCT增强DU145细胞株对DTX的药物敏感度,DU145对DTX的IC50明显降低[(24.55±0.36)vs.(11.85±0.25)nM,P﹤0.01]。联合用药组Caspase9(P﹤0.01)﹑Caspase3(P﹤0.05)表达增加,VEGFA表达下降(P﹤0.01),ABCB1的表达无变化。细胞迁移能力下降。结论 OCT增强DU145细胞株对DTX的药物敏感度,细胞迁移能力下降,这可能与Caspase9﹑Caspase3表达上调而VEGFA表达下调有关。Objective To investigate the effects and possible mechanisms of Octreotide on the drug sensitivity of Docetaxel resistant DU145 cells in vitro. Methods The inhibitory effects of Docetaxel, Octreotide and Octreotide(100nM) combined with Docetaxel at different concentrations on DU145 cell were tested by MTT assay. The following-up experiments were divided into four groups, control group, OCT(100nM) group, DTX(10nM)/OCT(100nM) group and DTX(10nM) group. The mRNA levels of Homo sapiens vascular endothelial growth factor A(VEGFA)﹑apoptosis-related cysteine peptidase(Caspase9)﹑caspase 3, apoptosisrelated cysteine peptidase(Caspase3) and ATP-binding cassette, sub-family B(MDR/TAP), member 1(ABCB1) in human prostate cancer cell line DU145 were detected by RT-PCR; The migration ability of cells in each group was detected by scratch test. Results The proliferation inhibitory rate of DU145 cell in DTX(10nM)/OCT(100nM) group[(55.70±0.08)%]was higher than that in Docetaxel [(26.23±0.03)%]or Octreotide group[(24.77±0.04)%],(P﹤0.01). Octreotide increased the drug sensitivity of DU145 cells against Docetaxel, with IC50 value decreasing significantly[(24.55±0.36) vs.(11.85±0.25)nM, P﹤0.01]. The gene expression of Caspase3 and Caspase9 in the drug combination group were higher than those in other groups, while the expression of VEGFA decreased in the drug combination group(P﹤0.01). In addition, there was no difference of ABCB1 mRNA level in all groups. The cell ability of migration in the combination group was lower than those in other groups. Conclusion The increased drug sensitivity and reduced migration ability of DU145 cell lines affected by Octreotide may be related to the increased expression of Caspase3 and Caspase9 and reduced expression of VEGFA.

关 键 词：多烯紫杉醇 奥曲肽 细胞增殖 细胞迁移 前列腺癌 

分 类 号：R73[医药卫生—肿瘤]