类胡萝卜素对人乳腺癌细胞增殖及bcl-2基因表达的影响

目的 观察类胡萝卜素对人乳腺癌MCF－7细胞存活率、细胞周期和凋亡,以及对凋亡相关基因bcl－2的影响。方法 用MTT检测类胡萝卜素对MCF－7细胞作用的时间效应和剂量效应;流式细胞仪观察类胡萝卜素处理人乳腺癌细胞后细胞周期以及细胞凋亡的改变。用RT－PCR检测凋亡相关基因bcl－2的变化。结果 6种结构不同的类胡萝卜素对MCF－7乳腺癌细胞展现出不同的增殖抑制效果,60μmol／L的β－胡萝卡素和番茄红素在第4天的抑制率分别为88．4％和87．8％,而玉米黄素、角黄素、虾青素和玉米黄素双棕榈酸酯的抑制作用较弱。类胡萝卜素并不诱导87．8％,而玉米黄素、角黄素、虾青素和玉米黄毒素双棕榈酸酯的抑制作用较弱。类胡萝卜素并不诱导MCF－7细胞凋亡,番茄红素可阻滞细胞周期于G1／M,玉米黄素双棕榈酸酯可阻滞细胞周期于G0／G1期,而其他类胡萝卡素并不影响细胞周期。类胡萝卜素可不同程度地下调凋亡相关基因bcl－2mRNA的表达,bcl－2基因的下调与类胡萝卜素的抑制作用呈较明显的相关性。结论 类胡萝卜素可直接抑制人乳腺癌细胞MCF－7的增殖,不同结构的类胡萝卜素可能具有不同的抑制机制。

The effects of carotenoids on the proliferation of human breast cancer cell and gene expression of bcl-2

OBJECTIVE: To investigate the effects of various carotenoids on the proliferation, cell cycle, apoptosis and expression of bcl-2 gene in breast cancer cell MCF-7. METHODS: Time and dose effects of individual carotenoids were detected using the MTT assay. The effects of individual carotenoids on cell cycle and the apoptosis were observed by flow cytometry. The expression of bcl-2 mRNA gene was detected using the RT-PCR method. RESULTS: All 4 carotenoids tested inhibited the proliferation of MCF-7 cell line, but with different potencies. beta-carotene and lycopene were the most active inhibitors (inhibition rate 88.2% and 87.8%, respectively) followed by zeaxanthin and astaxanthin. All 4 carotenoids did not induce cell apoptosis. Cell cycle progression was blocked at G(2)/M phase with 60 micromol/L lycopene and at G(0)/G(1) phase with 60 micromol/L zeaxanthin dipalmitate. Carotenoids down regulated bcl-2 gene expression. CONCLUSION: Carotenoids could inhibit the proliferation of human beast cancer MCF-7 cell line in vitro and the action of carotenoids may be worked through different pathways.