目的探讨4-羟苯基维胺(4-hydroxyphenyl-retinamide,4-HPR)对瘢痕疙瘩成纤维细胞的作用及PI3K/Akt信号转导通路的影响。方法通过免疫印迹方法检测人瘢痕疙瘩成纤维细胞中,4-HPR对Ⅰ型前胶原(type I pro-collagen,ProcollagenⅠ)和基质...目的探讨4-羟苯基维胺(4-hydroxyphenyl-retinamide,4-HPR)对瘢痕疙瘩成纤维细胞的作用及PI3K/Akt信号转导通路的影响。方法通过免疫印迹方法检测人瘢痕疙瘩成纤维细胞中,4-HPR对Ⅰ型前胶原(type I pro-collagen,ProcollagenⅠ)和基质金属蛋白酶-1(matrix metallo-protein-1,MMP-1)蛋白表达水平,观察4-HPR联合TGF-β1、PD98059、SP600125、SB203580及LY294002对瘢痕疙瘩成纤维细胞中相关蛋白表达的影响。结果瘢痕疙瘩成纤维细胞中,4-HPR使ProcollagenⅠ蛋白表达水平明显减少,MMP-1蛋白表达水平明显增加,并且具有4-HPR浓度依赖性(P<0.01)。在瘢痕疙瘩成纤维细胞中,4-HPR+TGF-β1组中ProcollagenⅠ蛋白表达水平较TGF-β1组明显降低(P<0.01),但P-Smad2和P-Smad3蛋白表达均无显著改变(P>0.05)。LY294002组中ProcollagenⅠ蛋白水平与对照组相比显著降低,MMP-1显著升高(P<0.01)。但PD98059、SB203580及SP600125组中ProcollagenⅠ和MMP-1蛋白水平与对照组相比未发生明显变化(P>0.05),且4-HPR可有效抑制P-Akt蛋白表达水平(P<0.01)。结论人瘢痕疙瘩成纤维细胞中,4-HPR可以抑制Ⅰ型前胶原蛋白的表达、上调MMP-1的表达,而这种调控作用可能与PI3K/Akt信号传导通路被削弱有关。展开更多
A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form re...A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form retinoyl chloride and then reacting with triethylamine to generate retinoyl ammonium salt which in turn is reacted with p-aminophenol to eventually produce 4-HPR. This process can overcome many scale-up challenges that exist in the methods reported in the literature and provide an easy, mild and high yield route for large scale synthesis of 4-HPR. Moreover, the effects of the molar ratios of the reagents on the yield are examined. The best molar ratios are a 2.0 molar equivalence of thionyl chloride and a 3.0 molar equivalence of paminophenol to retinoic acid, and the total yield is 80. 7%.展开更多
文摘目的探讨4-羟苯基维胺(4-hydroxyphenyl-retinamide,4-HPR)对瘢痕疙瘩成纤维细胞的作用及PI3K/Akt信号转导通路的影响。方法通过免疫印迹方法检测人瘢痕疙瘩成纤维细胞中,4-HPR对Ⅰ型前胶原(type I pro-collagen,ProcollagenⅠ)和基质金属蛋白酶-1(matrix metallo-protein-1,MMP-1)蛋白表达水平,观察4-HPR联合TGF-β1、PD98059、SP600125、SB203580及LY294002对瘢痕疙瘩成纤维细胞中相关蛋白表达的影响。结果瘢痕疙瘩成纤维细胞中,4-HPR使ProcollagenⅠ蛋白表达水平明显减少,MMP-1蛋白表达水平明显增加,并且具有4-HPR浓度依赖性(P<0.01)。在瘢痕疙瘩成纤维细胞中,4-HPR+TGF-β1组中ProcollagenⅠ蛋白表达水平较TGF-β1组明显降低(P<0.01),但P-Smad2和P-Smad3蛋白表达均无显著改变(P>0.05)。LY294002组中ProcollagenⅠ蛋白水平与对照组相比显著降低,MMP-1显著升高(P<0.01)。但PD98059、SB203580及SP600125组中ProcollagenⅠ和MMP-1蛋白水平与对照组相比未发生明显变化(P>0.05),且4-HPR可有效抑制P-Akt蛋白表达水平(P<0.01)。结论人瘢痕疙瘩成纤维细胞中,4-HPR可以抑制Ⅰ型前胶原蛋白的表达、上调MMP-1的表达,而这种调控作用可能与PI3K/Akt信号传导通路被削弱有关。
文摘A method to synthesize anticancer drug N-（ 4- hydroxyphenyl） retinamide （4-HPR）on a large scale is described. It consists of the preferred steps of reacting all-trans retinoic acid with thionyl chloride to form retinoyl chloride and then reacting with triethylamine to generate retinoyl ammonium salt which in turn is reacted with p-aminophenol to eventually produce 4-HPR. This process can overcome many scale-up challenges that exist in the methods reported in the literature and provide an easy, mild and high yield route for large scale synthesis of 4-HPR. Moreover, the effects of the molar ratios of the reagents on the yield are examined. The best molar ratios are a 2.0 molar equivalence of thionyl chloride and a 3.0 molar equivalence of paminophenol to retinoic acid, and the total yield is 80. 7%.
