摘要
目的:探讨他莫昔芬(TAM)与维甲酸(ATRA)联合对人乳腺癌他莫昔芬耐药株的作用。方法:在体外培养条件下,分别或联合应用ATRA和TAM作用于MCF-7人乳腺癌他莫昔芬耐药株(MCF-7/T)及敏感组(MCF-7/S)。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和FasL蛋白的变化。结果:TAM能抑制ER阳性MCF-7/S的生长,阻滞细胞周期于G0/G1期,并可诱导细胞凋亡,TAM不能抑制MCF-7/T的生长;ATRA预处理细胞24h后,TAM抗乳腺癌细胞MCF-7/S的作用增强,且恢复了MCF-7/T对TAM的敏感性。AT-RA与TAM联用后,MCF-7/T细胞Bcl-2蛋白表达下调,细胞Bax、Fas和FasL蛋白表达水平未见明显变化。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MCF-7/S作用;视黄酸能加强TAM对激素敏感细胞MCF-7/S的抗乳腺癌作用,恢复耐受细胞MCF-7/T对TAM的敏感性。同时恢复TAM对MCF-7/T的促凋亡作用。
OBJECTIVE：To investigate the combining anticancer effect of tamoxifen （TAM） and retinoic acid on Tamoxifen-resistant breast cancer cells lines in vitro.METHODS：MCF-7 ER-positive breast cancer cell lines were treated with tamoxifen alone,and in combination with retinoic acid 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.RESULTS：TAM inhibited the proliferation of ER-postive MCF-7/S with cell cycle arrest in G0/G1 phase and with induction of apoptosis.TAM did not inhibit MCF-7/T growth.Anticancer effect of TAM was enhanced when MCF-7/S were pretreated with retinoic acid for 24 hours,and MCF-7/T sensitivity to tamoxifen was restored.Bcl-2 protein expression was down-regulated by TAM and retinoic acid,but these drugs did not affect Bax,Fas,FasL protein expression.CONCLUSIONS：TAM has anticancer effect by inhibiting proliferation and inducing apoptosis in ER-positive MCF-7/S in vitro,and retinoic acid can enhance anticancer effect of TAM on MCF-7/S.MCF-7/T sensitivity to tamoxifen and the pro-apoptotic effect was restored after retinoic acid added.
出处
《中华肿瘤防治杂志》
CAS
2010年第18期1425-1428,共4页
Chinese Journal of Cancer Prevention and Treatment
