姜黄素衍生物抑制结肠癌细胞增殖侵袭作用

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1、分类号：R735.3密级：一般UDC：616-006编号：2009211911广州医学院硕士学位论文姜黄素衍生物抑制结肠癌细胞增殖侵袭作用研究生：何利兵崔博导师：张继民教授张继民教授申请学位级别:医学硕士医学硕士年级:二零零九级学科专业:外科学外科学研究方向:胃肠道肿瘤论文提交日期:2012年5月2012年5月论文答辩日期:2012年5月学位类型:临床医学专业学位临床医学学位授予单位:广州医学院答辩委员会主席:评议人:2012年5月广州医学院硕士学位论文姜黄素衍生物抑制结肠癌细胞增殖侵袭作用Therolesofcurcu

2、minderivativesintheproliferationandinvasionofhumancoloncancercelllineLovoandSW480研究生：何利兵导师：张继民教授专业：胃肠外科广州医学院2012年5月广州医学院硕士学位论文姜黄素衍生物抑制结肠癌细胞增殖侵袭作用目录中文摘要„„„„„„„„„„„„„„„„„„„„„„„„„„„„3英文摘要„„„„„„„„„„„„„„„„„„„„„„„„„„„„5前言„„„„„„„„„„„„„„„„„„„„„„„„„„„„„„7材料与方法„„„„„„„„„„„„

3、„„„„„„„„„„„„„„„10结果„„„„„„„„„„„„„„„„„„„„„„„„„„„„„„16讨论„„„„„„„„„„„„„„„„„„„„„„„„„„„„„„20参考文献„„„„„„„„„„„„„„„„„„„„„„„„„„„„23文献综述„„„„„„„„„„„„„„„„„„„„„„„„„„„„26致谢„„„„„„„„„„„„„„„„„„„„„„„„„„„„„„35学位论文原创声明„„„„„„„„„„„„„„„„„„„„„„„„36学位论文知识产权权属声明„„„„„„„„„„„„„„„„„„„„36关于学问论文使用

4、授权的说明„„„„„„„„„„„„„„„„„„„371广州医学院硕士学位论文姜黄素衍生物抑制结肠癌细胞增殖侵袭作用主要英文缩略语CurCurcumin姜黄素NF-κBNuclearfactor-kappa-B核转录因子TNF-αTumornecrosisfactor-alpha肿瘤坏死因子FBSFetalbovineserum胎牛血清NBSNew-bornbovineserum新生牛血清PBSPhosphatebuffersolution磷酸盐缓冲液ODOpticaldensity光密度PIPropidiumIodide

5、碘化丙啶DMSODimethylsulfoxide二甲基亚砜MTT3-[4,5-dimethylthylthiazol-2-yl]-2,5diphenyl-tetrazoliumbromide四甲基偶氮唑蓝IC50halfmaximalinhibitoryconcentrationofasubstance半抑制浓度2广州医学院硕士学位论文姜黄素衍生物抑制结肠癌细胞增殖侵袭作用姜黄素衍生物抑制结肠癌细胞增殖侵袭作用中文摘要姜黄素是从天然植物姜黄中提取的一种酚类化合物，具有抗炎及抗氧化双重作用。已有研究证实姜黄素通过抑制肿瘤

6、血管生成对多种人类肿瘤具有抑制作用。然而姜黄素水溶性差、易水解、不稳定，口服吸收后迅速被肝脏代谢，首过消除现象明显致使其生物利用度低；而姜黄素的衍生物能有效提其高生物利用度，增强抗肿瘤效能。本研究探讨姜黄素及其4种衍生物（T316、T62、T63、T6F4）对结肠癌细胞株Lovo和SW480增殖、迁移能力及诱导癌细胞凋亡能力的影响；并将姜黄素和4种衍生物的抗结肠癌作用进行了比较。目的：研究姜黄素（Curcumin，Cur）及其4种衍生物（T316、T62、T63、T6F4）对结肠癌细胞株Lovo和SW480的毒性作用及增

7、殖迁移能力的影响，并初步探讨其作用机制。方法：（1）利用低浓度（0.125μmol/L～32μmol/L）的姜黄素及4种衍生物作用于人结肠癌细胞株Lovo和SW48048h后，通过四甲基偶氮唑盐(MTT)比色检测姜黄素对这两株肿瘤细胞生长抑制能力的影响；（2）采用细胞划痕实验检测姜黄素及4种衍生物对人类两株结肠癌细胞24小时内迁移作用的影响；（3）利用软琼脂克隆实验检测姜黄素及4种衍生物对人类两株结肠癌细胞克隆增殖能力的影响；（4）PI单染流式细胞技术检测姜黄素及其4种衍生物对结肠癌细胞凋亡能力的影响；（5）荧光素酶报告

8、基因检测姜黄素及其4种衍生物对TNF-α诱导下结肠癌细胞内核转录因子（NF-κB）信号通路的影响。结果：0.125μmol/L～32μmol/L浓度范围内Cur对Lovo株和SW480株细胞的生长抑制率随药物的浓度升高而增大，呈剂量依赖关系；0.125μmol/L～10μmol/L浓度范围内T316、T62、T63、