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CK2抑制剂CX4945对肺癌A549/DDP细胞顺铂耐药性的逆转作用 被引量:5
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作者 金承基 宋萍 +2 位作者 郑金旭 孙金玲 徐莉莉 《肿瘤》 CAS CSCD 北大核心 2019年第1期10-18,40,共10页
目的 :探讨蛋白激酶CK2(casein kinase 2,曾称酪蛋白激酶Ⅱ)抑制剂CX4945对顺铂(cisplatin,DDP)耐药性肺癌A549/DDP细胞生长活性的影响及其可能的作用机制。方法 :CCK-8法检测肺癌A549细胞及其耐药性A549/DDP细胞的DDP半数抑制浓度(half... 目的 :探讨蛋白激酶CK2(casein kinase 2,曾称酪蛋白激酶Ⅱ)抑制剂CX4945对顺铂(cisplatin,DDP)耐药性肺癌A549/DDP细胞生长活性的影响及其可能的作用机制。方法 :CCK-8法检测肺癌A549细胞及其耐药性A549/DDP细胞的DDP半数抑制浓度(half maximal inhibitory concentration,IC50),以及抑制剂CX4945对A549/DDP细胞耐药性的影响。蛋白质印迹法检测A549及A549/DDP细胞在DDP干预前后Wnt信号通路相关蛋白(CK2α、β-catenin和cyclin D1)、耐药相关蛋白[多药耐药相关蛋白1(multidrug resistance-associated protein 1,MRP1)和肺耐药相关蛋白(lung resistance-related protein,LRP)]和凋亡相关蛋白[剪切型半胱天冬酶-3(cleaved caspase-3,c-caspase-3)]的表达变化。将A549/DDP细胞分为未处理对照组、CX4945组、DDP组及CX4945+DDP组,各组药物处理后,采用蛋白质印迹法和FCM法分别检测Wnt信号通路、耐药及凋亡相关蛋白的表达以及细胞凋亡情况。结果:DDP对A549/DDP细胞的IC50值是A549细胞的4.59倍,并在CX4945预处理后A549/DDP细胞耐药性明显降低(P <0.001)。与A549细胞相比,A549/DDP细胞中CK2α、β-catenin、cyclin D1、MRP1和LRP蛋白的表达水平明显较高,并在DDP处理后进一步升高(P值均<0.001);然而A549细胞中,DDP处理后CK2α、β-catenin和cyclin D1蛋白表达水平明显降低(P值均<0.01),而MRP1和LRP蛋白表达则无明显变化(P值均>0.05)。与未处理对照组和DDP组相比,CX4945组和CX4945+DDP组的A549/DDP细胞中β-catenin、cyclin D1、MRP1和LRP蛋白表达水平均明显降低(P值均<0.01)。此外,CX4945+DDP组的A549/DDP细胞凋亡率和c-caspase-3表达水平均较未处理对照组和DDP组明显升高(P值均<0.001)。结论 :CK2抑制剂CX4945可通过抑制Wnt通路,降低耐药相关蛋白的表达,从而逆转肺癌A549/DDP细胞的顺铂耐药性。 展开更多
关键词 非小细胞肺 抗药性 肿瘤 WNT信号通路 顺铂 酪蛋白激酶Ⅱ CX4945
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Hot deformation behavior of GH4945 superalloy using constitutive equation and processing map 被引量:4
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作者 Zhao-xia Shi Xiao-feng Yan +3 位作者 Chun-hua Duan Jin-gui Song Ming-han Zhao Jue Wang 《Journal of Iron and Steel Research International》 SCIE EI CAS CSCD 2017年第6期625-633,共9页
The hot deformation behavior of GH4945 superalloy was investigated by isothermal compression test in the temperature range of 1000--1200 ℃with strain rates of 0.001 10.000 s 1 toa total strain of 0.7. Dynamic recryst... The hot deformation behavior of GH4945 superalloy was investigated by isothermal compression test in the temperature range of 1000--1200 ℃with strain rates of 0.001 10.000 s 1 toa total strain of 0.7. Dynamic recrystallization is the primary softening mechanism for GH4945 superalloy during hot deformation. The constitutive equation is established, and the calculated apparent activation energy is 458. 446 kJ/moh The processing maps at true strains of 0.2, 0.4 and 0.6 are generally similar, dem- onstrating that strain has little influence on processing map. The power dissipation efficiency and in- stability factors are remarkably influenced by deformation temperature and strain rate. The optimal hot working conditions are determined in temperature range of 1082 -1131 ℃ with strain rates of 0.004--0.018 s-1. Another domain of1134--1150 ℃ and 0. 018 0.213s ^- can also be selected as the optimal hot working conditions. The initial grains are replaced by dynamically reerystallized ones in optimal domains. The unsafe domains locate in the zone with strain rates above 0, 274 s^- 1, mainly characterized by uneven microstructure. Hot working is not recommended in the unsafe domains. 展开更多
关键词 Hot deformation behaviorConstitutive equationProcessing mapGH4945 superalloy
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金松双黄酮联合CX-4945通过Notch1通路调控胶质母细胞瘤细胞增殖与凋亡的机制研究 被引量:2
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作者 连海伟 杨烁锐 刘仁忠 《国际肿瘤学杂志》 CAS 2022年第6期321-326,共6页
目的探究金松双黄酮联合CK2抑制剂CX-4945对脑胶质母细胞瘤U87细胞增殖与凋亡的影响及作用机制。方法体外培养脑胶质母细胞瘤U87细胞,分别用0.01、0.10、1.00、10.00、100.00 μmol/L浓度的金松双黄酮处理U87细胞;用1.25、2.50、5.00、1... 目的探究金松双黄酮联合CK2抑制剂CX-4945对脑胶质母细胞瘤U87细胞增殖与凋亡的影响及作用机制。方法体外培养脑胶质母细胞瘤U87细胞,分别用0.01、0.10、1.00、10.00、100.00 μmol/L浓度的金松双黄酮处理U87细胞;用1.25、2.50、5.00、10.00、20.00 μmol/L浓度的CX-4945处理U87细胞。将U87细胞分为对照组(不做任何处理)、金松双黄酮组(100.00 μmol/L金松双黄酮)、CX-4945组(5.00 μmol/L CX-4945)、金松双黄酮联合CX-4945组(100.00 μmol/L金松双黄酮+5.00 μmol/L CX-4945)。采用MTT法检测细胞存活率;Caspase3/7活力检测法和Annexin Ⅴ/ PI双染法检测细胞凋亡情况;蛋白质印迹法检测100.00 μmol/L金松双黄酮处理U87细胞后Notch1通路相关蛋白ICN1、HES1和DLL3表达情况。结果 0、0.01、0.10、1.00、10.00、100.00 μmol/L浓度的金松双黄酮处理U87细胞存活率分别为(100.00±6.30)%、(112.02±7.63)%、(140.84±6.73)%、(113.92±7.92)%、(102.60±7.12)%、(73.16±2.74)%,差异具有统计学意义(F=55.21,P<0.001);0 μmol/L与0.01、0.10、1.00、100.00 μmol/L浓度时的细胞存活率差异均具有统计学意义(P=0.009;P<0.001;P=0.003;P<0.001)。100.00 μmol/L浓度时的金松双黄酮可抑制U87细胞活性,而其他浓度则表现为U87细胞活性的增强或无明显作用。0、1.25、2.50、5.00、10.00、20.00 μmol/L浓度的CX-4945处理U87细胞存活率分别为(100.00±5.53)%、(108.70±10.24)%、(93.14±2.82)%、(81.46±4.92)%、(56.92±3.99)%、(31.24±2.67)%,差异具有统计学意义(F=135.18,P<0.001);0 μmol/L与1.25、5.00、10.00、20.00 μmol/L浓度时的差异均具有统计学意义(P=0.022;P<0.001;P<0.001;P<0.001)。低浓度(1.25 μmol/L)的CX-4945对U87细胞活性表现为增强,较高浓度(5.00、10.00、20.00 μmol/L)时表现为抑制。对照组、金松双黄酮组、CX-4945组及金松双黄酮联合CX-4945组U87细胞的存活率分别为(100.00±5.53)%、(71.96±2.10)%、(77.66±4.12)%、(42.56±4.22)%,差异具有统计学意义(F=160.56,P<0.001);对照组与各处理组间的差异均具有统计学意义(均P<0.001);金松双黄酮联合CX4945处理组与金松双黄酮组、CX-4945组差异均具有统计学意义(均P<0.001)。上述4组U87细胞的Caspase3/7活力分别为2.34±0.47、4.02±0.22、3.67±0.32、5.85±0.28,差异具有统计学意义(F=55.80,P<0.001);各组的细胞凋亡率分别为(0.40±0.10)%、(17.37±0.57)%、(3.00±0.66)%、(33.47±0.87)%,差异具有统计学意义(F=1 822.18,P<0.001);进一步两两比较发现,对照组与各处理组的Caspase3/7活力、细胞凋亡率差异均具有统计学意义(P<0.001,P=0.001,P<0.001;P<0.001,P=0.001,P<0.001);金松双黄酮联合CX4945组与金松双黄酮组、CX-4945组的Caspase3/7活力、细胞凋亡率差异均具有统计学意义(均P<0.001)。100.00 μmol/L金松双黄酮处理U87细胞后Notch1通路相关蛋白ICN1(0.55±0.07vs.1.01±0.09)、HES1(0.66±0.08vs.1.00±0.06)和DLL3(0.74±0.04vs.1.01±0.09)的蛋白相对表达量均降低,差异均具有统计学意义(t=5.94,P=0.004;t=5.15,P=0.007;t=4.00,P=0.016)。结论金松双黄酮可通过抑制Notch1信号通路,与CK2抑制剂CX-4945协同抑制胶质母细胞瘤U87细胞增殖,促进细胞凋亡。 展开更多
关键词 胶质母细胞瘤 细胞增殖 细胞凋亡 受体 Notch1 金松双黄酮 CX-4945
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Dark Matter Density Profiles of Selected Spiral Galaxies
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作者 Alberto Sadun Brittany Salmon +1 位作者 Conor Evans Masoud Asadi-Zeydabadi 《International Journal of Astronomy and Astrophysics》 2024年第3期172-183,共12页
Understanding the dark matter distribution throughout a galaxy can provide insight into its elusive nature. Numerous density profiles, such as the Navarro, Frenk and White model, have been created in an attempt to stu... Understanding the dark matter distribution throughout a galaxy can provide insight into its elusive nature. Numerous density profiles, such as the Navarro, Frenk and White model, have been created in an attempt to study this distribution through analyzing orbital velocities of luminous matter and modeling dark matter distributions to explain these observations. However, we are interested in a simple model to consider the significant fluctuations in rotation curves at larger radii. Therefore, our model is much simpler compared to those previously mentioned. Our model used all the observational data available for four selected galactic rotation curves. These data present a significant variation in the orbital velocity of matter at the same distances. By running real observational data through our model, we show that the density of the dark matter within them shows real complex structure, which is not suggested by other computational models. Our aim of this paper is to model this structure and then speculate as to the cause and implications of these density fluctuations. 展开更多
关键词 Dark Matter Density Galactic Rotation Curves Spiral Galaxies NGC 2841 NGC 4527 NGC 4945 NGC 3198
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Casein kinase 2 modulates the spindle assembly checkpoint to orchestrate porcine oocyte meiotic progression 被引量:1
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作者 Xiayan ShiYang Yilong Miao +4 位作者 Zhaokang Cui Yajuan Lu Changyin Zhou Yu Zhang Bo Xiong 《Journal of Animal Science and Biotechnology》 CAS CSCD 2020年第3期715-723,共9页
Background:CK2(casein kinase 2)is a serine/threonine-selective protein kinase that has been involved in a variety of cellular processes such as DNA repair,cell cycle control and circadian rhythm regulation.However,its... Background:CK2(casein kinase 2)is a serine/threonine-selective protein kinase that has been involved in a variety of cellular processes such as DNA repair,cell cycle control and circadian rhythm regulation.However,its functional roles in oocyte meiosis have not been fully determined.Results:We report that CK2 is essential for porcine oocyte meiotic maturation by regulating spindle assembly checkpoint(SAC).Immunostaining and immunoblotting analysis showed that CK2 was constantly expressed and located on the chromosomes during the entire oocyte meiotic maturation.Inhibition of CK2 activity by its selective inhibitor CX-4945 impaired the first polar body extrusion and arrested oocytes at M I stage,accompanied by the presence of BubR1 at kinetochores,indicative of activated SAC.In addition,we found that spindle/chromosome structure was disrupted in CK2-inhibited oocytes due to the weakened microtubule stability,which is a major cause resulting in the activation of SAC.Last,we found that the level DNA damage as assessed byγH2A.X staining was considerably elevated when CK2 was inhibited,suggesting that DNA damage might be another critical factor leading to the SAC activation and meiotic failure of oocytes.Conclusions:Our findings demonstrate that CK2 promotes the porcine oocyte maturation by ensuring normal spindle assembly and DNA damage repair. 展开更多
关键词 CK2 CX-4945 DNA damage Meiotic maturation Porcine oocytes Spindle assembly
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