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Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway

机译:Aclarubicin通过SIRT1 / PI3K / AKT信号通路调节胶质瘤细胞生长和DNA损伤

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Aclarubicin (ACR), an anthracycline anti-tumor agent, is known to play important roles in cancer. Evidence has suggested that ACR has therapeutic effects on rats intracranially implanted with C6 glioma cells. However, the function and mechanism of ACR in glioma cells remain elusive. In this study, we examined the effects of ACR on glioma cell growth, apoptosis, and DNA damage. Our results showed that treatment with different concentrations of ACR (1, 2, and 5 mu M) markedly impeded glioma cell survival, significantly decreased cell proliferation, and increased cell apoptosis and caspase-3 activity. Furthermore, ACR treatment promoted DNA damage through phosphorylation of ATM and CHK1 in U87 and U251 cells. Treatment with ACR also increased sirtuin 1 (SIRT1) expression and inhibited phosphatidylinositol 3 '-kinase (PI3K)/AKT pathway activation. Interestingly, we found that AKT overexpression reversed the effects of ACR on glioma cell survival, proliferation, apoptosis, and DNA damage. Thus, our data suggest that ACR induces apoptosis and DNA damage in U87 and U251 cells through the SIRT1/PI3K/AKT signaling pathway.
机译:众所周知,Aclarubicin(ACR),一种蒽环霉素抗肿瘤剂,可在癌症中起重要作用。证据表明ACR对颅内植入C6胶质瘤细胞的大鼠具有治疗效果。然而,ACR在胶质瘤细胞中的功能和机制仍然难以捉摸。在这项研究中,我们研究了ACR对胶质瘤细胞生长,细胞凋亡和DNA损伤的影响。我们的研究结果表明,不同浓度的ACR(1,2和5μm)的治疗明显地阻抗胶质瘤细胞存活,显着降低细胞增殖,以及增加的细胞凋亡和Caspase-3活性。此外,ACR治疗通过U87和U251细胞的ATM和CHK1的磷酸化促进DNA损伤。用ACR治疗也增加了SIRTUIN 1(SIRT1)表达和抑制磷脂酰肌醇3'-kin酶(PI3K)/ AKT途径活化。有趣的是,我们发现AKT过度表达逆转了ACR对胶质瘤细胞存活,增殖,细胞凋亡和DNA损伤的影响。因此,我们的数据表明ACR通过SIRT1 / PI3K / AKT信号通路诱导U87和U251细胞中的凋亡和DNA损伤。

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    《RSC Advances》 |2019年第49期|共8页
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  • 正文语种 eng
  • 中图分类 化学;
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