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首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.
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Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.

机译:具有UCN-01的丁酸钠对宫颈癌细胞具有明显的抗肿瘤活性。

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摘要

AIM: The effect of combining sodium butyrate (NaB), a histone deacetylase inhibitor, and 7-hydroxy-staurosporine (UCN-01) on cytotoxicity in human cervical carcinoma cells was evaluated. MATERIALS AND METHODS: HeLa and CaSki cells were treated using NaB alone or in combination with staurosporine (STS) or its analog UCN-01. Cytotoxicity was determined by flow cytometry and morphological assays. Apoptotic pathways were characterized by Western blotting and immunostaining. CaSki cells were also xenografted into nude mice to assess the in vivo effects of NaB/UCN-01 combination. RESULTS: Treatment with NaB and STS or UCN-01 resulted in enhanced apoptosis of cancer cells. Apoptosis involved mitochondrial pathways and overexpression of p53 and p73. In concordance, co-treatment modulated some p53/p73 downstream targets such as p21, BAX, BCL-2 and BCL-X(L), leading to increased caspase-3 and poly(ADP-ribose) polymerase cleavage. In vivo, NaB/UCN-01 combination exerted a substantial tumour growth suppression effect compared with single treatment. CONCLUSION: UCN-01 was shown to be a potentiator of NaB therapy for cervical cancer cells.
机译:目的:评估联合使用组蛋白脱乙酰基酶抑制剂丁酸钠(NaB)和7-羟基-星形孢菌素(UCN-01)对人宫颈癌细胞的细胞毒性的作用。材料与方法:单独使用NaB或与星形孢菌素(STS)或其类似物UCN-01组合使用HeLa和CaSki细胞。通过流式细胞术和形态学测定来确定细胞毒性。通过Western印迹和免疫染色来表征凋亡途径。还将CaSki细胞异种移植到裸鼠中,以评估NaB / UCN-01组合的体内作用。结果:用NaB和STS或UCN-01处理可增强癌细胞的凋亡。凋亡涉及线粒体途径和p53和p73的过度表达。一致地,共处理调节了一些p53 / p73下游靶标,例如p21,BAX,BCL-2和BCL-X(L),导致caspase-3和聚(ADP-核糖)聚合酶裂解增加。在体内,与单一治疗相比,NaB / UCN-01组合发挥了实质性的肿瘤生长抑制作用。结论:UCN-01被证明是NaB治疗子宫颈癌细胞的增强剂。

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