目的:探索肝癌缺失因子1(deleted in liver cancer 1,DLC-1)对耐恩杂鲁胺前列腺癌(prostate cancer,PCa)细胞增殖,侵袭和凋亡的影响以及作用机制。方法:体外以不同浓度的恩杂鲁胺药物培养人前列腺癌lncap及C4-2细胞株6个月以上,构建恩...目的:探索肝癌缺失因子1(deleted in liver cancer 1,DLC-1)对耐恩杂鲁胺前列腺癌(prostate cancer,PCa)细胞增殖,侵袭和凋亡的影响以及作用机制。方法:体外以不同浓度的恩杂鲁胺药物培养人前列腺癌lncap及C4-2细胞株6个月以上,构建恩杂鲁胺耐药细胞系lncap-R,C4-2-R。CCK-8法检测其IC50,验证恩杂鲁胺耐药株是否构建成功。利用慢病毒转染lncap-R,C4-2-R,以敲低和过表达DLC-1,采用克隆实验、Transwell实验和流式细胞术检测DLC-1对耐恩杂鲁胺的前列腺癌细胞的增殖、侵袭和凋亡的影响。结果:与对照组相比,过表达组DLC-1显著抑制了2个耐药株的增殖和侵袭进程。机制上,WB实验结果表明DLC-1表达与2个耐药株中Rho蛋白的表达呈负相关。Rho抑制剂rhosin逆转了因敲低DLC-1后lncap-R细胞凋亡减少的情况。结论:DLC-1可以下调耐药株中的Rho蛋白的表达,并抑制耐药株的增殖和侵袭。展开更多
A reaction for the synthesis of rothindin,a naturally occurring isoflavone glycoside,between the 7-hydroxy-3′,4′-methylenedioxyisoflavone(ψ-baptigenin),which are prepared in good yield from a Houben-Hoesch reaction...A reaction for the synthesis of rothindin,a naturally occurring isoflavone glycoside,between the 7-hydroxy-3′,4′-methylenedioxyisoflavone(ψ-baptigenin),which are prepared in good yield from a Houben-Hoesch reaction,and 1-bromo-2,3,4,6-tetra-O-acetyl——D-glucopyranose at the NaHCO3/KCl alkaline solutions in presence of the phase transfer catalyst tri(3,6-dioxaheptyl)amine(TDA-1) is discussed.The formation of the corresponding glucosides are confirmed by IR and 1HNMR studies,with a 82% yield of O-glycoside conjugate.展开更多
文摘目的:探索肝癌缺失因子1(deleted in liver cancer 1,DLC-1)对耐恩杂鲁胺前列腺癌(prostate cancer,PCa)细胞增殖,侵袭和凋亡的影响以及作用机制。方法:体外以不同浓度的恩杂鲁胺药物培养人前列腺癌lncap及C4-2细胞株6个月以上,构建恩杂鲁胺耐药细胞系lncap-R,C4-2-R。CCK-8法检测其IC50,验证恩杂鲁胺耐药株是否构建成功。利用慢病毒转染lncap-R,C4-2-R,以敲低和过表达DLC-1,采用克隆实验、Transwell实验和流式细胞术检测DLC-1对耐恩杂鲁胺的前列腺癌细胞的增殖、侵袭和凋亡的影响。结果:与对照组相比,过表达组DLC-1显著抑制了2个耐药株的增殖和侵袭进程。机制上,WB实验结果表明DLC-1表达与2个耐药株中Rho蛋白的表达呈负相关。Rho抑制剂rhosin逆转了因敲低DLC-1后lncap-R细胞凋亡减少的情况。结论:DLC-1可以下调耐药株中的Rho蛋白的表达,并抑制耐药株的增殖和侵袭。
文摘Wnt信号通路是一类以分泌型Wnt蛋白为配体激活的信号通路,主要包括经典Wnt/β-catenin信号通路和非经典Wnt/Ca 2+信号通路。大约10%~20%的转移性去势抵抗型前列腺癌(metastatic castration-resistant prostate cancer,mCRPC)患者体内存在Wnt信号通路调控基因的体细胞突变,主要包括CTNNB1和RSPO2的激活突变和APC、RNF43和ZNRF3的失活突变。近年来文献报道指出传统及新型内分泌治疗会诱发经典Wnt/β-catenin信号通路的活化,从而促使非雄激素依赖性前列腺癌细胞生长,另外,非经典Wnt/Ca 2+信号通路的活化也会导致机体对恩杂鲁胺在内的雄激素受体拮抗剂出现耐药。因此,目前理论上认为Wnt信号通路的活化可以降低新型内分泌制剂的治疗效果。对此,发表于2019年European Urology杂志上题为《Wnt-pathway activating mutations are associated with resistance to first-line abiraterone and enzalutamide in castration-resistant prostate cancer》基于临床肿瘤标本DNA测序结果,对存在Wnt信号通路的活化的mCRPC患者是否对一线药物阿比特龙或恩杂鲁胺产生耐药进行相关分析研究。
文摘A reaction for the synthesis of rothindin,a naturally occurring isoflavone glycoside,between the 7-hydroxy-3′,4′-methylenedioxyisoflavone(ψ-baptigenin),which are prepared in good yield from a Houben-Hoesch reaction,and 1-bromo-2,3,4,6-tetra-O-acetyl——D-glucopyranose at the NaHCO3/KCl alkaline solutions in presence of the phase transfer catalyst tri(3,6-dioxaheptyl)amine(TDA-1) is discussed.The formation of the corresponding glucosides are confirmed by IR and 1HNMR studies,with a 82% yield of O-glycoside conjugate.