OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the benefi...OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.展开更多
本研究采用AB-8大孔吸附树脂、半制备高效液相色谱对金露梅枝叶中槲皮素-7-O-β-D-葡糖苷酸提取分离,并通过13 C NMR鉴定其化学结构,最后采用以4-硝基酚-α-D-吡喃葡萄糖苷(pNPG)为底物的酶抑制剂筛选模型检测其对α-葡萄糖苷酶的抑制...本研究采用AB-8大孔吸附树脂、半制备高效液相色谱对金露梅枝叶中槲皮素-7-O-β-D-葡糖苷酸提取分离,并通过13 C NMR鉴定其化学结构,最后采用以4-硝基酚-α-D-吡喃葡萄糖苷(pNPG)为底物的酶抑制剂筛选模型检测其对α-葡萄糖苷酶的抑制活性和类型。结果显示:槲皮素-7-O-β-D-葡糖苷酸分布在20%乙醇大孔吸附树脂(AB-8)洗脱液中,采用半制备高效液相色谱和高效液相色谱分离纯化得槲皮素-7-O-β-D-葡糖苷酸2481.8 mg,纯度为97.95%。活性检测结果表明,槲皮素-7-O-β-D-葡糖苷酸对α-葡萄糖苷酶的最大抑制率为94.67%,IC 50为0.259 mmol/L,抑制率显著高于阳性对照药物阿卡波糖,且抑制剂类型为竞争性抑制。展开更多
适宜的株高和穗位高可提高植株的养分利用效率及抗倒伏性,对玉米增产和稳产具有重要意义。为揭示玉米株高和穗位高遗传机制,本研究以854份玉米自交系为关联群体,利用均匀分布于玉米10条染色体的2795个SNP标记对4个环境下玉米株高、穗位...适宜的株高和穗位高可提高植株的养分利用效率及抗倒伏性,对玉米增产和稳产具有重要意义。为揭示玉米株高和穗位高遗传机制,本研究以854份玉米自交系为关联群体,利用均匀分布于玉米10条染色体的2795个SNP标记对4个环境下玉米株高、穗位高以及穗位系数进行全基因组关联分析(genome-wide association study,GWAS)。共定位到81个显著关联SNP位点(P<0.0001),其中与株高显著关联的SNP为35个,单个位点表型解释率为0.02%~6.23%;与穗位高显著关联SNP为31个,单个位点表型变异解释率为0.03%~3.06%;与穗位系数显著关联的SNP位点为24个,单个位点表型变异解释率为0.03%~6.64%。进一步鉴定出15个可在2个及以上环境共定位的稳定SNP,其中6个为本研究首次发现,9个位于前人定位QTL区间或/和关联SNP位点2 Mb范围内。在15个稳定SNP位点上下游各200kb的置信区间共发现83个功能注释基因,结合文献分析筛选出了每个位点最有可能的候选基因,这些候选基因主要参与激素合成与信号转导、糖类代谢、细胞分裂调控等途径。鉴定出6个主效SNP位点,并发现1个可同时调控株高、穗位高和穗位系数的一因多效位点。本研究可为分子标记辅助选择育种提供有效遗传位点,为精细定位和克隆株高与穗位高相关性状基因提供参考。展开更多
基金The project supported by National Natural Science Foundation of China(81202840,81373815)Specialized Research Fund for the Doctoral Program of Higher Education of China(20131107110014)+1 种基金Beijing Natural Science Foundation(7162084)Swedish Cancer Foundation(150815)
文摘OBJECTIVE GubenyiliuⅡ(GYⅡ),a traditional Chinese medicine(TCM)formula used in our hospital,has shown beneficial effects in cancer patients.In this study,we investigated the molecular mechanisms underlying the beneficial effects of GYⅡon murine breast cancer models.METHODS Inhibition of tumor growth and metastasis was evaluated by assessment of tumor weight and analysis of bioluminescent signal after a homograft inoculation.Viability of cultured breast cancer cells was determined using MTT assay andreal-time cell analysis(RTCA).Cell migratory ability was evaluated by Transwell?assay and wound healing assay.Subsequently,the potential anti-tumor and anti-metastatic mechanism was investigated by Western blotting and Immunohistochemistry.RESULTS GYⅡshowed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model.And GYⅡsuppressed theproliferation of 4T1 and MCF-7 cells in a dose-dependent manner.A better inhibitory effect on 4T1 cells proliferation and migration was found in sub-fractions(SF)of GYⅡ.Moreover,heparanase expression and degree of angiogenesis were reduced in tumor tissues.Western blotting analysis showed decreased expression of heparanase and growth factors in the cells treated with GYⅡand its sub-fractions(SF2 and SF3),there by a reduction in phosphorylation of ERK and AKT.CONCLUSION GYⅡexerts anti-tumor growth and anti-metastatic effects on murine breast cancer model.Sub-fractions 2 and 3 exhibits higher potency of the anti-tumor activity that is,at least partly,associated with decreased heparanase and growth factor sexpression,which subsequently sup-pressed activation of ERK and AKT pathways.
文摘适宜的株高和穗位高可提高植株的养分利用效率及抗倒伏性,对玉米增产和稳产具有重要意义。为揭示玉米株高和穗位高遗传机制,本研究以854份玉米自交系为关联群体,利用均匀分布于玉米10条染色体的2795个SNP标记对4个环境下玉米株高、穗位高以及穗位系数进行全基因组关联分析(genome-wide association study,GWAS)。共定位到81个显著关联SNP位点(P<0.0001),其中与株高显著关联的SNP为35个,单个位点表型解释率为0.02%~6.23%;与穗位高显著关联SNP为31个,单个位点表型变异解释率为0.03%~3.06%;与穗位系数显著关联的SNP位点为24个,单个位点表型变异解释率为0.03%~6.64%。进一步鉴定出15个可在2个及以上环境共定位的稳定SNP,其中6个为本研究首次发现,9个位于前人定位QTL区间或/和关联SNP位点2 Mb范围内。在15个稳定SNP位点上下游各200kb的置信区间共发现83个功能注释基因,结合文献分析筛选出了每个位点最有可能的候选基因,这些候选基因主要参与激素合成与信号转导、糖类代谢、细胞分裂调控等途径。鉴定出6个主效SNP位点,并发现1个可同时调控株高、穗位高和穗位系数的一因多效位点。本研究可为分子标记辅助选择育种提供有效遗传位点,为精细定位和克隆株高与穗位高相关性状基因提供参考。
