姜黄素前体药物fm0806-1的体内外抗肿瘤作用及其在体肠吸收行为的分析-antitumor effect of curcumin prodrug fm 0806 - 1 in vivo and in vitro and analysis of its intestinal absorption behavior in vivo.docxVIP

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姜黄素前体药物fm0806-1的体内外抗肿瘤作用及其在体肠吸收行为的分析-antitumor effect of curcumin prodrug fm 0806 - 1 in vivo and in vitro and analysis of its intestinal absorption behavior in vivo.docx

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姜黄素前体药物fm0806-1的体内外抗肿瘤作用及其在体肠吸收行为的分析-antitumor effect of curcumin prodrug fm 0806 - 1 in vivo and in vitro and analysis of its intestinal absorption behavior in vivo

dose-dependent manner and influenced the morphology of cells. (3) The expressions of Hsp70, Bax protein were enhanced, while Hsp90, Erk1/2, P-Erk1/2 protein were decreased after the treatment of FM0806-1 containing serum. (4) FM0806-1 at dose of 25-100mg/kg showed significant inhibitory effect on H22 and S180 in mice models.There were significantly higher than the same dose of curcumin group. (5) FM0806-1 at dose of 40mg/kg showed significant inhibitory effect on CA46 nude mice xenograft model. (6) Drug has the physical adsorption in four intestinal segments to some extend(pH6.8). In three different pH, drug has different degrees of absorption in four intestina segments.Conclusion: (1) FM0806-1 have no cytotoxicity in vitro. It can release high concentrations of curcumin in vivo, suggesting a bright future as a Cur prodrug. (2) FM0806-1 has significant antitumor activity in vivo, which was higher than cur. But it has the physical adsorption to some extend, so its dosage forms need futher optimization.Key words: Curcumine; prodrug; antitumor activity; in situ intestinal absorption英文缩略词表AbbreviationsFull English NameChinese NameDMSOdimethylsulfoxide二甲基亚砜Erkextracellular signal-regulated protein kinase细胞外信号调节蛋白激酶PBSphosphate buffer saline磷酸盐缓冲液MTT3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐IC5050 % inhibition concentration50 %抑制浓度Curcurcumin姜黄素SDSsodium dodecyl sulfate十二烷基硫酸钠PVDFpoly vinylidene fluoride聚偏氟乙烯Hsp90Heat shock protein 90热休克蛋白90Hsp70Heat shock protein 70热休克蛋白70HRPHorseradish peroxidase辣根过氧化物酶SDSsodium dodecyl sulfate polyacrylamide gel electrophoresis十二烷基磺酸钠聚丙烯酰胺电泳HPLChigh performance liquid chromatography高效液相色谱法 TEMEDN,N,N,N-TetramethylethylenediamineN,N,N,N-四甲基乙二胺 PMSFPhenylmethanesulfonyl fluoride苯甲基磺酰氟DTTDL-Dithiothreitol二硫苏糖醇 EDTAEthylene Diamine Tetraacetic Acid乙二胺四乙酸 F68Poloxamer 188泊洛沙姆 188学位论文原创性声明和版权使用授权书学位论文原创性声明本人郑重声明：所呈交的学位论文，是本人在导师的指导下，独立进行研究工作所取得的真实成果。除文中已注明引用的内容外，本论文不含任何其他个人或集体已经发表或撰写过的作品成果。对本论文