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  

Combining anticancer effect of tamoxifen and γ-interferon on breast cancer in vitro and its mechanism

作　　者：高德宗[1] 高华[2] 郭秀会[1] 赵忠红[1] 余之刚[1] 

机构地区：[1]山东大学第二医院乳腺外科,山东济南250033 [2]山东省胸科医院呼吸内科,山东济南250013

出　　处：《中国普通外科杂志》2007年第11期1076-1080,共5页China Journal of General Surgery

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。Objective To investigate the combining anticancer effect of tamoxifen （ TAM ） and γ-interferon on breast cancer ceils 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 ceils 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.

关 键 词：乳腺肿瘤 ER阳性 Γ-干扰素 他莫昔芬 BCL-2 CASPASE-8 

分 类 号：R737.9[医药卫生—肿瘤]