[目的]通过分析中药活性成分对肿瘤相关的多条信号通路抑制作用的差异,研究对信号通路抑制作用存在互补现象的两个化合物熊果酸(ursolic acid,UA)和粉防己碱(tetrandrine,Tet)协同抗肿瘤增殖的作用及其最优配比。[方法]运用多信号通路...[目的]通过分析中药活性成分对肿瘤相关的多条信号通路抑制作用的差异,研究对信号通路抑制作用存在互补现象的两个化合物熊果酸(ursolic acid,UA)和粉防己碱(tetrandrine,Tet)协同抗肿瘤增殖的作用及其最优配比。[方法]运用多信号通路报告基因技术,研究5个具有抗肿瘤活性的化合物千金藤碱(cepharanthine,Cep)、Tet、18α-甘草酸(18α-glycyrrhetinic acid,18α-Gly)、UA、木犀草素(luteolin,Lut)对肿瘤相关的MAPK/ERK、MAPK/JNK、NF-κB、Wnt、Notch、Cell Cycle、Myc/Max以及Hypoxia信号通路活化程度的影响;采用MTT法和结晶紫法研究由Cep、Tet、18α-Gly、UA、Lut组成的15个不同化合物组合对人肿瘤细胞MDA-MB-231、SW480、MG63、PC3、DU145、HCT116、143B、MDA-MB-468的抗增殖作用;运用两药相互作用指数(coefficient of drug interaction,CDI)法筛选存在协同增效作用的化合物组合;采用等效线法和合用指数(combination index,CI)法筛选该组合协同抗肿瘤细胞增殖的最优配比。[结果]信号通路报告基因实验发现化合物组合UA+Tet对与肿瘤相关的8条信号通路活化的抑制作用存在互补,提示UA和Tet之间可能具有协同抗肿瘤细胞增殖作用。CDI法验证后发现UA和Tet具有协同抗肿瘤细胞增殖作用。等效线法、CI法分析得出UA与Tet最佳浓度比为9:1。[结论]UA、Tet对8条肿瘤相关信号通路具有抑制互补作用,用MTT、结晶紫等不同方法证实二者协同抗增殖作用,并筛选出UA和Tet的最优配比,这为研发抗癌复方提供了新的思路。展开更多
NANOG has been extensively researched since its discovery by Chambers et al. NANOG is a homeodomain transcription factor and an essential regulator of embryonic stem cell(ESC) self-renewal, which inhibits differentiat...NANOG has been extensively researched since its discovery by Chambers et al. NANOG is a homeodomain transcription factor and an essential regulator of embryonic stem cell(ESC) self-renewal, which inhibits differentiation. Cancer stem cells(CSCs) are a small subset of cells that are thought to drive uncontrolled tumor growth; CSCs retain the tumor capabilities of self-renewal and propagation. The existence of CSCs was recently shown by direct experimental evidence. NANOG is expressed in CSCs and ESCs, although it remains unclear whether ESCs and CSCs share similar mechanisms in the regulation of physical and biological processes. Several studies suggest that the expression level of NANOG is high in cancer tissues and low or absent in normal tissues. High levels of NANOG expression are associated with advanced stages of cancer and a poor prognosis, indicating that it plays a vital role in tumor transformation, tumorigenesis, and tumor metastasis. NANOG is part of a complex regulatory network that controls cell fate determination, proliferation, and apoptosis. NANOG cooperates with other regulators, such as microflora, transcription factors, and kinases, in cancer cells. NANOG might have a promising future in anti-cancer and other therapeutic treatments, which could improve human health.展开更多
文摘[目的]通过分析中药活性成分对肿瘤相关的多条信号通路抑制作用的差异,研究对信号通路抑制作用存在互补现象的两个化合物熊果酸(ursolic acid,UA)和粉防己碱(tetrandrine,Tet)协同抗肿瘤增殖的作用及其最优配比。[方法]运用多信号通路报告基因技术,研究5个具有抗肿瘤活性的化合物千金藤碱(cepharanthine,Cep)、Tet、18α-甘草酸(18α-glycyrrhetinic acid,18α-Gly)、UA、木犀草素(luteolin,Lut)对肿瘤相关的MAPK/ERK、MAPK/JNK、NF-κB、Wnt、Notch、Cell Cycle、Myc/Max以及Hypoxia信号通路活化程度的影响;采用MTT法和结晶紫法研究由Cep、Tet、18α-Gly、UA、Lut组成的15个不同化合物组合对人肿瘤细胞MDA-MB-231、SW480、MG63、PC3、DU145、HCT116、143B、MDA-MB-468的抗增殖作用;运用两药相互作用指数(coefficient of drug interaction,CDI)法筛选存在协同增效作用的化合物组合;采用等效线法和合用指数(combination index,CI)法筛选该组合协同抗肿瘤细胞增殖的最优配比。[结果]信号通路报告基因实验发现化合物组合UA+Tet对与肿瘤相关的8条信号通路活化的抑制作用存在互补,提示UA和Tet之间可能具有协同抗肿瘤细胞增殖作用。CDI法验证后发现UA和Tet具有协同抗肿瘤细胞增殖作用。等效线法、CI法分析得出UA与Tet最佳浓度比为9:1。[结论]UA、Tet对8条肿瘤相关信号通路具有抑制互补作用,用MTT、结晶紫等不同方法证实二者协同抗增殖作用,并筛选出UA和Tet的最优配比,这为研发抗癌复方提供了新的思路。
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2011HM021
文摘NANOG has been extensively researched since its discovery by Chambers et al. NANOG is a homeodomain transcription factor and an essential regulator of embryonic stem cell(ESC) self-renewal, which inhibits differentiation. Cancer stem cells(CSCs) are a small subset of cells that are thought to drive uncontrolled tumor growth; CSCs retain the tumor capabilities of self-renewal and propagation. The existence of CSCs was recently shown by direct experimental evidence. NANOG is expressed in CSCs and ESCs, although it remains unclear whether ESCs and CSCs share similar mechanisms in the regulation of physical and biological processes. Several studies suggest that the expression level of NANOG is high in cancer tissues and low or absent in normal tissues. High levels of NANOG expression are associated with advanced stages of cancer and a poor prognosis, indicating that it plays a vital role in tumor transformation, tumorigenesis, and tumor metastasis. NANOG is part of a complex regulatory network that controls cell fate determination, proliferation, and apoptosis. NANOG cooperates with other regulators, such as microflora, transcription factors, and kinases, in cancer cells. NANOG might have a promising future in anti-cancer and other therapeutic treatments, which could improve human health.
