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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 effect of tamoxifen (TAM) combined with retinoic acid (ATRA) on the resistance of human breast cancer tamoxifen. Methods: MCF-7 human breast cancer cell line MCF-7 / T and MCF-7 / S were treated with ATRA and TAM respectively in vitro or in vitro. The cell growth inhibition was analyzed by MTT assay. The cell cycle distribution, apoptosis rate and the changes of Bcl-2, Bax, Fas and FasL protein were detected by flow cytometry (FCM). TAM could inhibit the growth of ERF-positive MCF-7 / S cells, arrest the cell cycle in G0 / G1 phase and induce apoptosis. TAM could not inhibit the growth of MCF-7 / T cells. After treated with ATRA for 24 h, The effect of TAM on breast cancer cells MCF-7 / S was enhanced and the sensitivity of MCF-7 / T to TAM was restored. After combination of AT-RA and TAM, the expression of Bcl-2 protein in MCF-7 / T cells was down-regulated while there was no significant change in Bax, Fas and FasL protein expression. CONCLUSION: In vitro, TAM exerts anti-ER positive MCF-7 / S effect by affecting cell cycle and inducing apoptosis. Retinoic acid can enhance the anti-breast cancer effect of TAM on hormone sensitive cell MCF-7 / S and restore Tolerance to cell sensitivity of MCF-7 / T to TAM. At the same time restore TAM on MCF-7 / T pro-apoptotic effect.