fh535抑制胰腺癌细胞生长转移的机制分析 word格式.docxVIP

FH535抑制胰腺癌细胞生长转移的机制研究中文摘要目的：Wnt/β-catenin 信号通路在胰腺癌等多种肿瘤的发生发展中起重要作用，经典 Wnt 信号通路的小分子抑制剂 FH535 能够抑制结肠癌、肺癌、乳腺癌和肝癌的生长转移， 对于胰腺癌的作用尚未见报道。本研究拟检测 FH535 对胰腺癌细胞转移及生长的作 用并研究其分子机制，为 Wnt/β-catenin 信号通路靶向的胰腺癌的治疗提供理论基础。方法：1、胰腺癌细胞系 PANC-1 及 BxPC-3 经不同浓度的 FH535 处理。2、应用 Western blot 法及双荧光素酶报告基因实验检测 FH535 对 Wnt/β-catenin通路的影响。3、应用划痕实验检测 FH535 对胰腺癌细胞迁移能力的影响。4、应用 Transwell 侵袭实验检测 FH535 对胰腺癌细胞侵袭能力的影响。5、应用粘附实验检测 FH535 对胰腺癌细胞粘附能力的影响。6、应用 MTT 法、平板克隆实验检测 FH535 对胰腺癌细胞生长的影响。7、应用流式细胞术检测 FH535 对胰腺癌细胞周期的影响。8、应用 Microarray 技术检测 FH535 对调控细胞生长转移基因的表达的影响。 结果：1、FH535 能够抑制胰腺癌细胞中 Wnt/β-catenin 信号通路的活性。2、FH535 能够抑制胰腺癌细胞的迁移能力。3、FH535 能够抑制胰腺癌细胞的侵袭能力。4、FH535 能够抑制胰腺癌细胞的粘附能力。5、FH535 能够阻滞细胞周期于 G2/M 期，并抑制胰腺癌细胞的生长。 结论：FH535 能够通过抑制细胞的迁移、侵袭、粘附能力显著抑制胰腺癌细胞转移，通 过诱导 G2/M 期周期阻滞抑制胰腺癌细胞增殖，提示 FH535 可能应用于胰腺癌的治中文摘要FH535 抑制胰腺癌细胞生长和转移的机制研究疗。关键词：胰腺癌，FH535，β-catenin，转移，生长作者：田亚丽 指导教师：陶敏教授FH535 inhibited matastasis and growth of pancreatic cancer cellsAbstractObjective:FH535 is a small molecule inhibitor of Wnt/β-catenin signaling pathway which has been proved by substantial evidences to be activated in various cancers, including pancreatic cancer. Activaiton of Wnt/β-catenin pathway plays an important role in tumor progression and metastasis. In this study, we investigated the inhibitory effect of FH535 on metastasis and growth of pancreatic cancer cells, and explored the mechanisms underlying. Our present study may provide a basis for further development of FH535 as a promising therapeutic agent for the treatment of pancreatic cancer.Methods:1．PANC-1 and BxPC-3 pancreatic cancer cells were treated with different concentrations of FH535.2．The effect of FH535 on the activity of Wnt/β-catenin pathway was investigatedusing western blots and luciferase reporter gene assays3．The effect of FH535 on the migration of pancreatic cancer cells was measured by in vitro wound-healing assay.4．The effect of FH535 on the invasion of pancreatic cancer cells was investigatedusing transwell assays.5．The effect of FH535 on the