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ROS-Dependent Cell Death Induced by Parthenolide in Human Hepatoma Cell HepG2

机译:苯酚对人肝癌HepG2细胞的ROS依赖性细胞死亡

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摘要

With the increase of the action time and dosing concentration, the proliferation of HepG2 cell was inhibited and its vitality gradually decreased. FCM showed that, with the increase of PN action time, the MMP gradually decreased; calcium ions flowed inwards; the cell cycle was arrested in phase G1; the cell apoptosis rate, especially late apoptosis and necrotic cells, increased. The shear expression of apoptosis-related proteins caspase3 and caspase9 was up-regulated; the shear expression of AIF, MIF and PARP1 proteins associated with Caspase-independent apoptosis, i.e. Parthanatos apoptosis, showed time-dependent up-regulation; the long and short expressions of anti-apoptosis protein FLIP showed different degrees of decrease; the ex-pression of autophagy-related proteins LC3A/B and becin-1 was up-regulated; the expression of P62 protein was down-regulated; the expression of cycle- related proteins P53, P27 and P21 increased significantly; the expression of CyclinD1 and CyclinE1 decreased. FCM was used to detect the increase of ROS with the action time of PN; and its generation level showed an increasing trend; after the combination with ROS scavenger NAC, there was no significant difference in cell viability with the control group. There was no significant difference in the expression level of relevant cell death protein with DMSO control group. There was no difference in intracellular ROS generation level with the control group. Conclusion: PN induces the ROS generation in HepG2 cell, blocks its cycle and causes apoptosis and au-tophagy to play an anti-tumor effect.,
机译:随着作用时间和剂量的增加,HepG2细胞的增殖受到抑制,其活力逐渐降低。 FCM显示,随着PN作用时间的增加,MMP逐渐降低;钙离子向内流动;细胞周期停在G1期。细胞凋亡率,尤其是晚期凋亡和坏死细胞增加。凋亡相关蛋白caspase3和caspase9的剪切表达上调。与半胱天冬酶非依赖性凋亡相关的AIF,MIF和PARP1蛋白的剪切表达,即Parthanatos凋亡,表现出时间依赖性上调;抗凋亡蛋白FLIP的长短表达出现不同程度的下降。自噬相关蛋白LC3A / B和becin-1的表达上调; P62蛋白表达下调;周期相关蛋白P53,P27和P21的表达明显增加; CyclinD1和CyclinE1的表达下降。 FCM检测PN随作用时间的增加而增加。世代水平呈上升趋势。与ROS清道夫NAC组合后,与对照组相比,细胞活力无明显差异。与DMSO对照组相比,相关细胞死亡蛋白的表达水平无明显差异。与对照组相比,细胞内ROS的产生水平没有差异。结论:PN诱导HepG2细胞中ROS的产生,阻断其循环并引起细胞凋亡和自噬,从而发挥抗肿瘤作用。

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