The anticancer activity of non-alkaloid components in Uncaria macrophylla Wall. was studied. The results indicated that ursolic acid showed the strongest activity of inhibiting the proliferation of tumor cells; 3β-6...The anticancer activity of non-alkaloid components in Uncaria macrophylla Wall. was studied. The results indicated that ursolic acid showed the strongest activity of inhibiting the proliferation of tumor cells; 3β-6β-23-trihydroxyurs-12-en-28-oic acid, β-sitosterol and 3β-6β-19α-trihydroxyurs-12-en-28-oic acid possessed the same activity, too.展开更多
目的研究防己生物碱类活性成分逆转乳腺癌阿霉素耐药潜在的作用机制。方法首先通过TCMSP数据库对防己生物碱类活性成分进行筛选,采用SwissTargetPrediction数据库在线预测防己生物碱类活性成分潜在靶点,通过GeneCards数据库收集疾病靶点...目的研究防己生物碱类活性成分逆转乳腺癌阿霉素耐药潜在的作用机制。方法首先通过TCMSP数据库对防己生物碱类活性成分进行筛选,采用SwissTargetPrediction数据库在线预测防己生物碱类活性成分潜在靶点,通过GeneCards数据库收集疾病靶点,取交集构建“成分-靶点”和蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,然后进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后对预测的防己生物碱类活性成分与核心靶点进行分子对接验证。进一步通过体外实验验证防己生物碱类活性成分抗肿瘤活性,采用CCK-8实验检测防己生物碱类活性成分对乳腺癌MCF-7、MCF-7/ADR细胞的增殖抑制作用,采用倒置光学显微镜、荧光显微镜检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞形态的影响,采用流式细胞仪检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞凋亡的影响,采用Western blotting检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞核心靶点蛋白表达的影响。结果N-甲基毛果芸香碱、光千金藤碱、粉防己碱和甜菜碱为逆转乳腺癌阿霉素耐药的防己生物碱类活性成分,可能作用于原癌基因SRC、表皮生长因子受体(epidermal growth factor receptor,EGFR)、热休克蛋白90α家族A类成员1(heat shock protein 90 alpha family class A member 1,HSP90AA1)、蛋白激酶B1(protein kinase b1,AKT1)、有丝分裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、磷脂酰肌醇激酶-3催化亚单位α基因(phosphatidylinositol 3-kinase catalytic alpha polypeptide gene,PIK3CA)、半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)等靶点,调控钙信号通路、环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)-cGMP依赖性蛋白激酶(cGMP dependent protein kinase,PKG)信号通路、Apenlin信号通路、维甲酸诱导基�展开更多
文摘The anticancer activity of non-alkaloid components in Uncaria macrophylla Wall. was studied. The results indicated that ursolic acid showed the strongest activity of inhibiting the proliferation of tumor cells; 3β-6β-23-trihydroxyurs-12-en-28-oic acid, β-sitosterol and 3β-6β-19α-trihydroxyurs-12-en-28-oic acid possessed the same activity, too.
文摘目的研究防己生物碱类活性成分逆转乳腺癌阿霉素耐药潜在的作用机制。方法首先通过TCMSP数据库对防己生物碱类活性成分进行筛选,采用SwissTargetPrediction数据库在线预测防己生物碱类活性成分潜在靶点,通过GeneCards数据库收集疾病靶点,取交集构建“成分-靶点”和蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,然后进行基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后对预测的防己生物碱类活性成分与核心靶点进行分子对接验证。进一步通过体外实验验证防己生物碱类活性成分抗肿瘤活性,采用CCK-8实验检测防己生物碱类活性成分对乳腺癌MCF-7、MCF-7/ADR细胞的增殖抑制作用,采用倒置光学显微镜、荧光显微镜检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞形态的影响,采用流式细胞仪检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞凋亡的影响,采用Western blotting检测防己生物碱类活性成分对MCF-7、MCF-7/ADR细胞核心靶点蛋白表达的影响。结果N-甲基毛果芸香碱、光千金藤碱、粉防己碱和甜菜碱为逆转乳腺癌阿霉素耐药的防己生物碱类活性成分,可能作用于原癌基因SRC、表皮生长因子受体(epidermal growth factor receptor,EGFR)、热休克蛋白90α家族A类成员1(heat shock protein 90 alpha family class A member 1,HSP90AA1)、蛋白激酶B1(protein kinase b1,AKT1)、有丝分裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、磷脂酰肌醇激酶-3催化亚单位α基因(phosphatidylinositol 3-kinase catalytic alpha polypeptide gene,PIK3CA)、半胱氨酸天冬氨酸蛋白酶-3(cystein-asparate protease-3,Caspase-3)等靶点,调控钙信号通路、环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)-cGMP依赖性蛋白激酶(cGMP dependent protein kinase,PKG)信号通路、Apenlin信号通路、维甲酸诱导基�
