他莫昔芬与γ-干扰素联合抗人乳腺癌细胞株的作用及其机制研究
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Combining anticancer effect of tamoxifen and γ-interferon on breast cancer in vitro and its mechanism
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    摘要:

    目的: 探讨他莫昔芬(TAM)与 γ-干扰素(γ-IFN)联合抗乳腺癌细胞株的作用及其机制。
    方法:在体外培养条件下,分别或联合应用γ-IFN,TAM或雌二醇(E2)作用于ER阳性的MCF-7人乳腺癌细胞株,用MTT比色法分析细胞生长抑制作用;用流式细胞仪(FCM)检测细胞周期分布、凋亡率及用药前后Bcl-2,Bax,Fas,FasL及Caspase-8蛋白的变化;荧光分光光度仪检测Caspase-3活性。
    结果:TAM能抑制ER阳性乳腺癌细胞的生长,阻滞细胞周期于G0/G1期,并可诱导细胞凋亡;同时,TAM能拮抗外源性雌激素对MCF-7细胞的促生长作用。γ-IFN预处理细胞24h后,TAM抗乳腺癌细胞的作用增强。联用γ-IFN与TAM后,细胞Bcl-2蛋白表达下调,Caspase-8表达上调;但药物处理前后,细胞Bax,Fas,FasL蛋白表达水平及Caspase-3活性未见明显变化。
    结论:体外条件下,TAM通过影响细胞周期、诱导细胞凋亡而发挥抗ER阳性乳腺癌细胞作用;γ-IFN能加强TAM的抗乳腺癌作用。两者作用机制可能系通过下调Bcl-2表达和上调Caspase-8的表达。

    Abstract:

    Abstract:Objective:To investigate the combining anticancer effect of tamoxifen (TAM) and γ-interferon on breast cancer cells in vitro and its mechanism.
    Methods :MCF-7 ER-positive breast cancer cell lines were treated with tamoxifen alone, or in combination with γ-interferon and/or estrogen in vitro. Cell proliferation was evaluated by MTT assay; FCM was used to determine the distribution of cell cycle,cell apoptosis and protein expression of Bcl-2,Bax,Fas,FasL,Caspase-8,and the activity of Caspase-3.
    Results:TAM inhibited the proliferation of ER-postive breast cancer cells with cell cycle arrest in G0/G1 phase and with induction of apoptosis,and the proliferation-promoting effect of estrogen on MCF-7 was blocked by TAM. Anticancer effect of TAM was enhanced when cells were pretreated with γ-interferon for 24 hours. Bcl-2 protein expression was down-regulated and Caspase-8 was up-regulated by TAM and/or γ-interferon, but these drugs did not affect Bax,Fas,FasL protein expression and the activity of Caspase-3.
    Conclusions:TAM has anticancer effect by inhibiting proliferation and inducing apoptosis in ER-positive breast cancer cells in vitro, and γ-interferon can enhance anticancer effect of TAM on breast cancer cells. The mechanism of these effects may be related with the down-regulation of Bcl-2 expression and up-regulation of Caspase-8 by TAM and γ-interferon.

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高德宗, 高华, 郭秀会, 赵忠红, 余之刚.他莫昔芬与γ-干扰素联合抗人乳腺癌细胞株的作用及其机制研究[J].中国普通外科杂志,2007,16(11):14-108.
DOI:10.7659/j. issn.1005-6947.2007.11.014

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  • 在线发布日期: 2007-11-25