研究背景:AMPK是細胞重要的能量感受器,控制細胞能量代謝以及分解代謝路徑。近年來,AMPK已經(jīng)成為腫瘤預防和治療的靶點之一,激活AMPK蛋白能抑制腫瘤細胞增殖。本課題主要分兩部分進行:1、氯胍抗腫瘤作用和機制;2、苯乙雙胍衍生物類AMPK激活劑構(gòu)效關(guān)系定量分析。研究方法:本課題選用UMUC3、T24和A549三種癌細胞系。MTT實驗檢測細胞增殖、克隆形成實驗和劃痕實驗分別用于檢測氯胍對癌細胞集落形成和遷移的影響。Western blot實驗檢測氯胍對AMPK信號通路的影響。利用文獻獲得54種苯乙雙胍類似物的IC50值并建立2D模型�；衔锓殖�2組,其中40個化合物用于建模,余下的14個化合物用于對已建模型的測試。利用40個化合物進行結(jié)構(gòu)定量分析并建立2D模型,利用該模型對余下的14個化合物進行分子對接以及分子描述,結(jié)果表明所有化合物都符合Lipinski五規(guī)則。實驗結(jié)果:氯胍對呈劑量依賴性抑制3種癌細胞系增殖、克隆形成以及遷移。Western blot結(jié)果表明氯狐激活AMPK信號通路。所有建模組化合物滿足Lipinski五規(guī)則,由40個建�；衔锏幕貧w分析得到的線性相關(guān)圖顯示出良好的...

【文章頁數(shù)】：72 頁

【學位級別】：碩士

【文章目錄】：
ABSTRACT
中文摘要
CHAPTER 1 INTRODUCTION
CHAPTER 2 MATERIALS AND METHODS
    2.1 EXPERIMENTAL MATERIALS
        2.1.1 REAGENTS AND KITS
        2.1.2 MAIN CONSUMABLES
        2.1.3 EXPERIMENTAL EQUIPMENT
        2.1.4 MAIN COMPUTER SOFTWARES
        2.1.5 CELL LINES
    2.2 CELL EXPERIMENT METHOD
        2.2.1 Preparation of reagents for cell culture
        2.2.2 Cell Recovery
        2.2.3 Cell Culture and Subculture
        2.2.4 Cell freezing
        2.2.5 Cell Count
        2.2.6 MTT assay for cell proliferation
        2.2.7 Cell Cloning Experiment
        2.2.8 Protein Expression Detection
    2.3 QSAR of Phenformin Derivatives
        2.3.1 Data Collection and Molecule Preparation
        2.3.2 QSAR study
        2.3.3 ADME Study
        2.3.4 Molecular Docking
CHAPTER 3 RESULTS
    3.1 Proguanil inhibits bladder cancer cell lines proliferation better than Metformin andPhenformin
    3.2 Proguanil suppresses colony formation
    3.3 Proguanil inhibits the migration of cells
    3.4 Proguanil modulates anti-proliferative effect through the AMPK pathway
    3.5 QSAR Study
    3.6 ADME STUDY
    3.7 MOLECULAR DOCKING
CHAPTER 4 DISCUSSION
CHAPTER 5 CONCLUSION
REFERENCES
PAPERS PUBLISHED DURING MY STUDY
ACKNOWLEDGEMENT



本文編號：3901819