Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and ...Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and A549 cells were treated with crizotinib. The inhibition of proliferation was quantitated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay. Apoptosis was quantified by flow cytometry. Expression of key proteins of the HGF/c-Met signaling pathway was examined by western blotting. In vivo, H1993 and A549 tumor cell xenograft models were established. Immunohistochemical analysis was used to determine protein expression of HGF and c-MET and the amount of phospho-c-MET(p-c-Met). Real-time quantitative polymerase chain reaction(PCR) was applied to examine the messenger RNA(m RNA) expression of c-MET and serine/threonine protein kinase(AKT). The expression and activation of the key proteins were evaluated by western blotting.Results In vitro, the growth of H1993, H2228, and A549 cells was inhibited after crizotinib treatment for 72 h. Apoptotic rates of H1993 and H2228 cells increased with the crizotinib concentration and exposure time. In vivo, the growth-inhibitory rate of crizotinib for H1993 xenografts was 72.3%. Positive expression rates of HGF and c-MET in H1993 xenografts were higher than those in A549 xenografts; the p-c-MET amount was the largest in H1993 xenograft control but the lowest in the H1993 xenograft with crizotinib treatment. The m RNA expression levels of c-MET and AKT in H1993 xenografts were higher than those of A549 xenografts. The protein levels of c-MET, AKT, and extracellular regulated protein kinases(ERK) in H1993 xenografts were higher than those in A549 xenografts; the p-AKT amount was higher in H1993 xenograft control than in A549 xenografts; the largest amount of p-c-MET was detected in H1993 xenograft control; the amount of p-ERK was the lowest in the H1993 xenograft with crizotinib treatment.Conclusion The HGF/c-Met signaling pathway may mediate crizotinib-induced apoptosis and inhibition of proliferation of lung adenocarcinoma cells.展开更多
级联H桥型高压变频器在轧钢、冶金、矿井提升、机车牵引以及电力系统有源滤波和无功功率补偿等场合都得到了广泛的应用。在6 k V及以上的工业应用场合,采用级联H桥型技术方案构成的变频器在成本、可靠性、电压谐波质量等方面具有相当的...级联H桥型高压变频器在轧钢、冶金、矿井提升、机车牵引以及电力系统有源滤波和无功功率补偿等场合都得到了广泛的应用。在6 k V及以上的工业应用场合,采用级联H桥型技术方案构成的变频器在成本、可靠性、电压谐波质量等方面具有相当的竞争性。在级联H桥型变频器中,各H桥单元的电压处于浮动状态,出于高压隔离的目的,一般采用光纤传输驱动脉冲信号。由于变频器中H桥单元个数众多,驱动脉冲数量庞大,为减少光纤使用数量,降低系统成本,提高系统可靠性,采用一条光纤信号进行脉冲传输成为一种可行的技术方案。分析了对脉冲信号进行编解码的技术方案,并将其成功应用于一台6 k V,600 k W高压变频器中,实验结果验证了所提的脉冲编解码方案的正确性与可行性。展开更多
目的观察柚皮苷对去卵巢骨质疏松大鼠骨组织HIF-1α/VEGF信号通路和H型血管形成的影响,探讨柚皮苷防治骨质疏松症的作用机制。方法建立去卵巢骨质疏松大鼠模型(随机将36只大鼠分为去卵巢组、假手术组和柚皮苷治疗组)。柚皮苷治疗3个月后...目的观察柚皮苷对去卵巢骨质疏松大鼠骨组织HIF-1α/VEGF信号通路和H型血管形成的影响,探讨柚皮苷防治骨质疏松症的作用机制。方法建立去卵巢骨质疏松大鼠模型(随机将36只大鼠分为去卵巢组、假手术组和柚皮苷治疗组)。柚皮苷治疗3个月后,检测血清和骨髓上清骨代谢指标和HIF-1α/VEGF信号通路变化,检测骨密度(bone mineral density,BMD)、骨微结构及H型血管变化。结果柚皮苷治疗组大鼠血清中成骨代谢指标[骨特异性碱性磷酸酶(BALP)、骨钙素(BGP)、I型原胶原分子N端前肽(PINP)]升高;而骨吸收标志物血清C端交联肽(CTX)降低;HIF-1α在血清和骨髓上清中表达均升高;VEGF在骨髓上清中表达升高,而血清中无明显改变;BMD和Micro-CT结果显示柚皮苷治疗组大鼠骨密度和骨量增加;同时股骨近端H型血管表达升高。结论柚皮苷可以调节骨代谢,改善骨质疏松大鼠骨密度,发挥抗骨质疏松作用,其作用机制可能是通过调节HIF-1α/VEGF信号通路、促进H型血管形成来实现的。展开更多
基金Supported by grants from the National Natural Sciences Foundation of China(No.81060188 and No.81260351)Guangxi Sciense&Technology Development Funds(No.2015139 and No.201017)
文摘Objective This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.Methods In vitro, H2228, H1993, and A549 cells were treated with crizotinib. The inhibition of proliferation was quantitated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay. Apoptosis was quantified by flow cytometry. Expression of key proteins of the HGF/c-Met signaling pathway was examined by western blotting. In vivo, H1993 and A549 tumor cell xenograft models were established. Immunohistochemical analysis was used to determine protein expression of HGF and c-MET and the amount of phospho-c-MET(p-c-Met). Real-time quantitative polymerase chain reaction(PCR) was applied to examine the messenger RNA(m RNA) expression of c-MET and serine/threonine protein kinase(AKT). The expression and activation of the key proteins were evaluated by western blotting.Results In vitro, the growth of H1993, H2228, and A549 cells was inhibited after crizotinib treatment for 72 h. Apoptotic rates of H1993 and H2228 cells increased with the crizotinib concentration and exposure time. In vivo, the growth-inhibitory rate of crizotinib for H1993 xenografts was 72.3%. Positive expression rates of HGF and c-MET in H1993 xenografts were higher than those in A549 xenografts; the p-c-MET amount was the largest in H1993 xenograft control but the lowest in the H1993 xenograft with crizotinib treatment. The m RNA expression levels of c-MET and AKT in H1993 xenografts were higher than those of A549 xenografts. The protein levels of c-MET, AKT, and extracellular regulated protein kinases(ERK) in H1993 xenografts were higher than those in A549 xenografts; the p-AKT amount was higher in H1993 xenograft control than in A549 xenografts; the largest amount of p-c-MET was detected in H1993 xenograft control; the amount of p-ERK was the lowest in the H1993 xenograft with crizotinib treatment.Conclusion The HGF/c-Met signaling pathway may mediate crizotinib-induced apoptosis and inhibition of proliferation of lung adenocarcinoma cells.
文摘级联H桥型高压变频器在轧钢、冶金、矿井提升、机车牵引以及电力系统有源滤波和无功功率补偿等场合都得到了广泛的应用。在6 k V及以上的工业应用场合,采用级联H桥型技术方案构成的变频器在成本、可靠性、电压谐波质量等方面具有相当的竞争性。在级联H桥型变频器中,各H桥单元的电压处于浮动状态,出于高压隔离的目的,一般采用光纤传输驱动脉冲信号。由于变频器中H桥单元个数众多,驱动脉冲数量庞大,为减少光纤使用数量,降低系统成本,提高系统可靠性,采用一条光纤信号进行脉冲传输成为一种可行的技术方案。分析了对脉冲信号进行编解码的技术方案,并将其成功应用于一台6 k V,600 k W高压变频器中,实验结果验证了所提的脉冲编解码方案的正确性与可行性。
文摘目的观察柚皮苷对去卵巢骨质疏松大鼠骨组织HIF-1α/VEGF信号通路和H型血管形成的影响,探讨柚皮苷防治骨质疏松症的作用机制。方法建立去卵巢骨质疏松大鼠模型(随机将36只大鼠分为去卵巢组、假手术组和柚皮苷治疗组)。柚皮苷治疗3个月后,检测血清和骨髓上清骨代谢指标和HIF-1α/VEGF信号通路变化,检测骨密度(bone mineral density,BMD)、骨微结构及H型血管变化。结果柚皮苷治疗组大鼠血清中成骨代谢指标[骨特异性碱性磷酸酶(BALP)、骨钙素(BGP)、I型原胶原分子N端前肽(PINP)]升高;而骨吸收标志物血清C端交联肽(CTX)降低;HIF-1α在血清和骨髓上清中表达均升高;VEGF在骨髓上清中表达升高,而血清中无明显改变;BMD和Micro-CT结果显示柚皮苷治疗组大鼠骨密度和骨量增加;同时股骨近端H型血管表达升高。结论柚皮苷可以调节骨代谢,改善骨质疏松大鼠骨密度,发挥抗骨质疏松作用,其作用机制可能是通过调节HIF-1α/VEGF信号通路、促进H型血管形成来实现的。
