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Bortezomib is a novel proteasome inhibitor, which has been successfully used to treat mantle cell lymphoma and multiple myeloma. However, the direct effects of bortezomib on acute promyelocytic leukaemia (APL) have not been fully investigated. In the present study, the WST-8 assay, western blotting, flow cytometry, monodansylcadaverine staining and transmission electron microscopy were performed. It was demonstrated that bortezomib treatment induced a time- and dose-dependent decrease in the viability of NB4 cells. Bortezomib treatment induced cell apoptosis in NB4 cells, as assessed by Annexin V/propidium iodide analysis, and the detection of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, Bax and Bcl-2 expression. Furthermore, bortezomib treatment induced autophagy in NB4 cells, as indicated by autophagosome formation, p62 degradation, LC3-I to LC3-II conversion and formation of acidic autophagic vacuoles. Notably, autophagy induced by bortezomib was initiated prior to apoptosis. Inhibition of autophagy by knocking down Beclin-1 expression increased bortezomib-induced apoptosis in NB4 cells. Therefore, the present study revealed that the combination of bortezomib and autophagy inhibition may be a potential treatment strategy for APL. 相似文献
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Lei Yang You-Ling Shi Yan Ma Wei-Wei Ren Guang-Ming Pang Jiao Liu 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2022,130(1):43-52
Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis. 相似文献
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目的比较手术夹闭和介入栓塞治疗颅内未破裂动脉瘤的安全性和有效性。方法计算机检索1990至2018年颅内未破裂动脉瘤的所有临床对照研究。两名研究员分别纳入研究、提取数据、质量评价并应用Rev Man5. 0软件进行数据处理。结果最终纳入21篇文献,病例数109114例。Meta分析结果提示:手术夹闭组动脉瘤闭塞率为88. 2%,平均住院时间7. 7天,均高于介入栓塞组的65. 3%和4. 1天,P 0. 05。介入组患者的短期死亡率和致残率分别为0. 61%和2. 1%,均低于手术组的1. 27%和4. 7%,P 0. 05。介入组患者的1年期死亡率和致残率(2. 5%、2. 5%)均与手术组(2. 2%、1. 8%)无明显差异,P 0. 05。漏斗图未发现发表偏倚。敏感性分析结果一致。结论介入栓塞相比于手术夹闭可缩短患者的住院时间,降低患者的短期不良预后发生率。但是动脉瘤的闭塞率较低,1年期预后与手术夹闭无明显差异。据此推测手术夹闭患者的长期预后可能要好于介入栓塞,手术夹闭更适合于年轻患者。 相似文献