β-胡萝卜素抑制MCF-7细胞生长上调过氧化酶体增殖物激活受体γ(PPARγ)表达

β-Carotene Inhibits Cell Viability and Up-regulates Peroxisome Proliferator-activated Receptor γ(PPARγ) Expression in MCF-7 Breast Cancer Cells

为了研究过氧化酶体增殖物激活受体γ(PPARγ)表达在β-胡萝卜素影响乳腺癌MCF-7细胞活力中所起的作用,采用MTT法测定细胞活力、Western印迹检测细胞中PPARγ的蛋白质水平,用RT-PCR从mRNA水平检测细胞内PPARγ、P21WAF1/CIP1、COX-2和P27表达.研究发现,β-胡萝卜素显著抑制人乳腺癌细胞株MCF-7细胞的生长,β-胡萝卜素对细胞生长的抑制作用呈现出时间和计量依赖关系;β-胡萝卜素能够呈现时间效应地从mRNA和蛋白质水平显著上调PPARγ的表达,β-胡萝卜素能够通过PPARγ调节P21WAF1/CIP1和COX-2 mRNA水平;PPARγ的抑制剂GW9662和抗氧化剂还原型谷胱甘肽(GSH)都能部分阻止由β-胡萝卜素引起的细胞活力下降.研究结果提示,激活PPARγ途径和调制细胞氧化状态是β-胡萝卜素对乳腺癌细胞MCF-7的生长抑制效应原因之一.

Whether the function of carotenoids on breast cell growth is mediated by peroxisome proliferatoractivated receptor γ （PPARγ） signaling pathway remained largely unknown. We tested the PPAR γ expression for the inhibition of MCF-7 human breast cancer cells under the treatments of β-carotene. The cell viability was determined by MTT assay, PPARγ protein expression was analyzed by Westem blotting and the mRNA levels of PPARγ, P21^WAF1/CIP1, COX-2, and P27 were evaluated by RT-PCR. The results showed that β-carotene inhibited the proliferation of MCF-7 cells in a dose- and time-dependent manner. β-Carotene exposure significantly up-regnlated the PPARγ mRNA level and protein expression in time-dependently. β-Carotene was also able to modulate P21^WAF1/CIP1 and COX-2 mRNA levels dependent to PPART. Pre-ineubation with PPARγ antagonist GW9662 and reduced glutathione （GSH） partly rescued the loss of cells. It suggested that the enhancement of PPARγ expression and the modulation of intercellular redox status may be a cause of MCF-7 cell growth inhibition by β-carotene.