吉西他滨联合雷公藤甲素治疗胰腺癌作用的体外实验研究-外科学(普通外科)专业论文.docxVIP

万方数据 万方数据 目 录 中文摘要············································3 英文摘要············································4 前 言············································6 材料与方法··········································8 结 果············································15 讨 论············································22 结 论············································26 参考文献············································26 致 谢············································31 文献综述············································32 2 吉西他滨联合雷公藤甲素治 疗 胰 腺 癌 作 用 的 体 外 实 验 研 究 中文摘要 目的 目前因为缺乏有效的治疗方法导致胰腺癌总体生存率很低，吉西他滨是胰腺 癌化疗的一线药物，但总体效果不佳，本研究通过联合吉西他滨（Gemcitabine,GEM） 与雷公藤甲素（Triptolide， TPL） 作用于胰腺癌细胞株AsPC-1以探讨雷公藤甲素 能否增强吉西他滨对胰腺癌细胞的诱导凋亡作用。 方法 MTT法测定比较吉西他滨、雷公藤甲素以及雷公藤甲素联合吉西他滨对AsPC-1 细胞的增殖抑制效果；Western Bloting方法检测凋亡相关蛋白caspase-3及PARP表 达的变化；流式细胞仪方法分析各实验组细胞凋亡比例的差别。 结果 TPL、GEM对AsPC-1细胞均具有明显的抑制增殖作用，并且呈剂量及时间相关 性。 GEM 对 AsPC-1 细 胞 的 48h IC50 为 720.67 ± 5.67ng/ml ， 72h IC50 为 174.07 ± 3.35ng/ml；TPL对 AsPC-1细胞48h IC50为14.23±1.45ng/ml，72h IC50为1.69± 0.24ng/ml，TPL与GEM联合应用于AsPC-1细胞，两药具有一定的协同性；48h后活化 的caspase-3表达量，联合用药组与各单药组及对照组比较，具有明显差别（P＜ 0.01)，各单药组与对照组比较亦有明显差别（P＜0.01)。48h后裂解的PARP表达量， 联合用药组与各单药组及对照组比较，具有明显差别（P＜0.01)，TPL单药组及GEM 单药组与对照组比较具有明显差别（P＜0.01)。24h后联合用药组、TPL单药组、GEM 单药组与对照组比较，细胞凋亡比例差别有明显统计学意义（P＜0.01)，联合用药 组与GEM单药组、TPL单药组比较有统计学意义（P＜0.01)；48h后联合用药组、TPL 单药组、GEM单药组与对照组比较，细胞凋亡比例有明显差别（P＜0.01)，联合用药 组与GEM单药组、TPL单药组比较（P＜0.01)；GEM与TPL两药抑制率为（0.5-1）时两 药联合的协同参数（CI）值为1.262-4.8944。 结论TPL对AsPC-1细胞具有明显的抑制细胞增殖及诱导凋亡活性；GEM与TPL联合用 于AsPC-1细胞具有协同抑制增殖效果。TPL可增强GEM对AsPC-1细胞的诱导凋亡作用。 【关键词】雷公藤甲素、吉西他滨、胰腺癌、增殖、凋亡 3 The effect of Gemcitabine combined with Triptolide on pancreatic cancer in vitro Abstract Objective The lack of effective treatment for pancreatic cancer results in a very low survival rate.Gemcitabine is the first-line drug on the chemotherapy of pancreatic cancer, but the overall effect is poor.This study explores the enhancement of the therapeutic effect on human pancreatic cancer cell line AsPC-1 via the combination of gemcit