Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melano...Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16 F-10 cells in to C57 BL/6 mice. Metastatic mice treated with two different doses of crocin（250 and 500 μg/kg of bodyweight） for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase（γ-GGT）, sialic acid,tumor necrosis factor alpha（TNF-a）, interleukin 10（IL-10）, IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases（MMPs）, extracellular regulated kinase 2（ERK2）, vascular endothelial growth factor（VEGF）, and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice.Further, in-vitro adhesion, invasion and migration of B16 F-10 cells were examined after 24 hours of crocin（5 and 10μg/mL） treatment. Administration of crocin to tumor bearing C57 BL/6 mice reduced the lung metastasis by 85%.Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and y-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2,K-ras, and VEGF. Crocin reduced the ability of B16 F-10 cells invasion（P〈0.05）, migration（P〈0.05） and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.展开更多
目的探讨ERK5(extracellular-regulated kinase5)MAPK(mitogen-activated protein kinase)信号转导通路与genistein对人乳腺癌细胞MDA-MB-231增殖抑制作用的关系。方法采用噻唑蓝(MTT)比色法检测genistein对MDA-MB-231增殖的抑制作用;...目的探讨ERK5(extracellular-regulated kinase5)MAPK(mitogen-activated protein kinase)信号转导通路与genistein对人乳腺癌细胞MDA-MB-231增殖抑制作用的关系。方法采用噻唑蓝(MTT)比色法检测genistein对MDA-MB-231增殖的抑制作用;采用流式细胞仪检测细胞凋亡情况;应用western blot分别检测ERK5总蛋白和凋亡相关蛋白Bax、Caspase3的表达。结果genistein对MDA-MB-231细胞增殖有明显的抑制作用;流式细胞仪检测到细胞产生凋亡;western blot分析提示genistein抑制ERK5总蛋白的表达,促进Bax和Caspase3蛋白表达。结论genistein可以影响ERK5MAPK信号转导通路,使凋亡相关蛋白表达增加,抑制MDA-MB-231细胞增殖。展开更多
目的:探讨坎地沙坦改善机械刺激诱导的心肌细胞肥大的效应及机制。方法:体外培养新生大鼠心肌细胞,接种在特制的硅胶皿上。按数字编码随机分为对照组、机械刺激组和机械刺激+坎地沙坦干预组。牵张硅胶皿(延伸120%)30 min构建机械刺激诱...目的:探讨坎地沙坦改善机械刺激诱导的心肌细胞肥大的效应及机制。方法:体外培养新生大鼠心肌细胞,接种在特制的硅胶皿上。按数字编码随机分为对照组、机械刺激组和机械刺激+坎地沙坦干预组。牵张硅胶皿(延伸120%)30 min构建机械刺激诱导的心肌细胞肥大模型,以3 H掺入法检测各组心肌细胞蛋白合成率,α-MHC免疫荧光染色以激光共聚焦成像测算心肌细胞表面积。以Real-time PCR和Western-Blot检测心肌细胞中心房利钠肽(ANP),骨骼肌α-肌动蛋白(SAA)基因和磷酸化细胞外调节蛋白激酶(ERKs)表达变化。结果:坎地沙坦显著改善了机械刺激所致的心肌细胞表面积(1.78±0.13 vs 3.16±0.28,P<0.05)和蛋白合成率(4.15±0.44 vs 6.75±0.71,P<0.05)增加以及ANP(2.21±0.27 vs 4.1±0.93,P<0.05)和SAA(5.45±0.6 vs 7.4±1.43,P<0.05)的表达上调,也显著降低了机械刺激诱导的ERKs磷酸化(3.85±0.33 vs 6.68±0.86,P<0.05)。结论:坎地沙坦可通过抑制ERKs磷酸化改善机械刺激诱导的心肌细胞肥大反应。展开更多
文摘Crocus sativus and its bioactive constituent crocin are well known for anti-tumor potential in different models.However, the efficacy of crocin on in-vivo melanoma metastasis is not yet reported. In this study, melanoma metastatic model was developed by tail vein injection of B16 F-10 cells in to C57 BL/6 mice. Metastatic mice treated with two different doses of crocin（250 and 500 μg/kg of bodyweight） for 10 days and parameters such as lung metastasis inhibition, mean survival time, lung hydroxyproline, uronic acid and hexosamine levels were analyzed after 21 days of treatment. Then blood was collected and serum gamma glutamyl transpeptidase（γ-GGT）, sialic acid,tumor necrosis factor alpha（TNF-a）, interleukin 10（IL-10）, IL-6, IL-2, and TIMP-1 levels were measured. Further, a lung histological examination was done in crocin treated metastatic mice. Subsequently hallmark metastatic parameters such as matrix metalloproteinases（MMPs）, extracellular regulated kinase 2（ERK2）, vascular endothelial growth factor（VEGF）, and K-ras gene expression were investigated in the lungs of crocin treated metastatic mice.Further, in-vitro adhesion, invasion and migration of B16 F-10 cells were examined after 24 hours of crocin（5 and 10μg/mL） treatment. Administration of crocin to tumor bearing C57 BL/6 mice reduced the lung metastasis by 85%.Elevated levels of hydroxyproline, uronic acid, hexosamine, serum sialic acid and y-GGT in metastatic control were found to be significantly reduced in crocin treated mice. Crocin also inhibited expression of MMP-2, MMP-9, ERK-2,K-ras, and VEGF. Crocin reduced the ability of B16 F-10 cells invasion（P〈0.05）, migration（P〈0.05） and adhesion by upregulating E-cadherin expression. In conclusion, crocin elicited marked anti-metastatic potential by regulating the metastasis induced biomarkers.
基金supported by grants from the Canadian Institute of Health Research(MOP-62923)University of Manitoba Graduate Fellowship,Natural Science Foundation of China(30770971&81070362)Natural Science Foundation of Hunan Province,P.R.China(11JJ2049)
文摘目的:探讨坎地沙坦改善机械刺激诱导的心肌细胞肥大的效应及机制。方法:体外培养新生大鼠心肌细胞,接种在特制的硅胶皿上。按数字编码随机分为对照组、机械刺激组和机械刺激+坎地沙坦干预组。牵张硅胶皿(延伸120%)30 min构建机械刺激诱导的心肌细胞肥大模型,以3 H掺入法检测各组心肌细胞蛋白合成率,α-MHC免疫荧光染色以激光共聚焦成像测算心肌细胞表面积。以Real-time PCR和Western-Blot检测心肌细胞中心房利钠肽(ANP),骨骼肌α-肌动蛋白(SAA)基因和磷酸化细胞外调节蛋白激酶(ERKs)表达变化。结果:坎地沙坦显著改善了机械刺激所致的心肌细胞表面积(1.78±0.13 vs 3.16±0.28,P<0.05)和蛋白合成率(4.15±0.44 vs 6.75±0.71,P<0.05)增加以及ANP(2.21±0.27 vs 4.1±0.93,P<0.05)和SAA(5.45±0.6 vs 7.4±1.43,P<0.05)的表达上调,也显著降低了机械刺激诱导的ERKs磷酸化(3.85±0.33 vs 6.68±0.86,P<0.05)。结论:坎地沙坦可通过抑制ERKs磷酸化改善机械刺激诱导的心肌细胞肥大反应。
