Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol.
Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol.
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DOI：
10.1186/1471-2407-8-391
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发表时间：
2008-12-29
期刊：
影响因子：
3.8
通讯作者：
Yuan J
中科院分区：
文献类型：
--
作者：
Androic I;Krämer A;Yan R;Rödel F;Gätje R;Kaufmann M;Strebhardt K;Yuan J
细胞周期蛋白B1是细胞周期蛋白依赖性激酶1（Cdk 1）的调节亚基，在细胞从G2期向有丝分裂期的转变中起重要作用。细胞周期蛋白B1经常被发现在原发性乳腺癌和宫颈癌细胞以及癌细胞系中过表达。其表达与妇科恶性肿瘤的恶性程度有关。为了探索周期蛋白B1作为妇科肿瘤治疗的潜在靶点，我们研究了小干扰RNA（small interfering RNA，siRNA）对不同妇科肿瘤细胞株的增殖率、细胞周期、蛋白表达和活性、凋亡诱导和集落形成的影响。使用小鼠异种移植模型检查体内肿瘤形成。下调细胞周期蛋白B1可抑制几种乳腺癌和宫颈癌细胞系的增殖，包括MCF-7、BT-474、SK-BR-3、MDA-MB-231和HeLa。结合细胞周期蛋白B1 siRNA与紫杉醇，我们观察到一个增加的凋亡率伴随着乳腺癌细胞的抗增殖作用增强。此外，对照HeLa细胞进行性生长，而HeLa细胞的细胞周期蛋白B1 siRNA预处理的肿瘤生长在裸鼠中被强烈抑制，表明细胞周期蛋白B1是体内肿瘤生长所必需的。我们的数据支持周期蛋白B1的概念是必不可少的生存和妇科癌细胞的增殖。一致地，敲低细胞周期蛋白B1抑制体外以及体内增殖。此外，靶向细胞周期蛋白B1使乳腺癌细胞对紫杉醇敏感，这表明特异性细胞周期蛋白B1靶向是与妇科癌症治疗中常规使用的药物组合的有吸引力的策略。
Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.
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影响因子：
7.8
作者：
Jin, P;Hardy, S;Morgan, DO
通讯作者：
Morgan, DO
整联蛋白和神经酰胺信号通路的激活可以抑制人类乳腺癌细胞系中胰岛素样生长因子I（IGF-I）的有丝分裂作用。
影响因子：
8.8
作者：
Perks, C M;Gill, Z P;Newcomb, P V;Holly, J M
通讯作者：
Holly, J M
影响因子：
11.2
作者：
Shen, ML;Feng, YD;Gong, JP
通讯作者：
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DOI：
10.1073/pnas.96.5.2147
发表时间：
1999-03-02
影响因子：
11.1
作者：
Innocente, SA;Abrahamson, JLA;Lee, JM
通讯作者：
Lee, JM
影响因子：
3.3
作者：
Taylor, WR;DePrimo, SE;Stark, GR
通讯作者：
Stark, GR