Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model
Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model
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DOI：
10.1002/ijc.23938
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发表时间：
2009-01-15
影响因子：
6.4
通讯作者：
Thompson, Alastair M.
中科院分区：
文献类型：
--
作者：
Appleyard, Maria Virginia C. L.;O'Neill, Mary A.;Thompson, Alastair M.
我们试图确定在不增加毒性的情况下，塞利西利(CyC202，R-rocovitine)是否能在不增加毒性的情况下，在All MCF7乳腺癌移植模型中增加阿霉素的抗肿瘤作用。将塞利康联合阿霉素与单用阿霉素或塞利康对MCF7细胞和裸鼠移植瘤的疗效进行了比较。用细胞周期分析、免疫组织化学和实时荧光定量聚合酶链式反应检测治疗后的细胞和肿瘤。在不增加小鼠毒性的情况下，Seliclib显著增强了阿霉素的抗肿瘤作用。MIB1(Ki67)免疫组织化学显示治疗后细胞增殖减少。与未治疗的对照组相比，阿霉素或塞利西利单独或联合治疗后，p21和p27的水平升高。而P53蛋白(DO1、CM1)、Survivin或P53磷酸化(SER15)在治疗组与对照组相比无明显变化。总之，CDK抑制剂seliclib(R-rocovitine)在不增加毒性的情况下增强了阿霉素在MCF7肿瘤中的抗肿瘤作用，其机制涉及细胞周期停滞而不是细胞凋亡。(C)2008年Wiley-Liss，Inc.
We sought to determine whether seliciclib (CYC202, R-roscovitine) could increase the antitumor effects of doxortibicin, with no increase in toxicity, in ail MCF7 breast cancer xenograft model. The efficacy of seliciclib combined with doxorubicin was compared with single agent doxorubicin or seliciclib administered to MCF7 cells and to nude mice hearing established MCF7 xenografts. Post-treatment cells and tumors were examined by cell cycle analysis, immunohistochemistry and real-time PCR. Seliciclib significantly enhanced the antitumor effect of doxorubicin without additional murine toxicity. MIB1 (ki67) immunohistochemistry demonstrated reduced proliferation with treatment. The levels of p21 and p27 increased after treatment with doxorubicin or seliciclib alone or in combination, compared to untreated controls. However, no changes in p53 protein (DO1, CM1), survivin or p53 phosphorylation (SER15) were observed in treated tumors compared with controls. In conclusion, the CDK inhibitor seliciclib (R-roscovitine) enhances the antitumor effect of doxortibicin in MCF7 tumors without increased toxicity with a mechanism that involves cell cycle arrest rather than apoptosis. (c) 2008 Wiley-Liss, Inc.