Yu Zeng-li, Zhang Li-shi, Wu De-sheng
School of Public School, Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2005 Sep;39(5):328-31.
To explore the effects of zearalenone (ZEA) on proliferation and apoptosis in estrogen-dependent human breast cancer MCF-7 cells and the likely underlying molecular mechanisms.
Cell viability was determined by MTT assay and cell cycle distribution by cytometry. Apoptosis was detected by Cell Death Detection ELISA and cytometry, respectively. The expressions of bax and bcl-2 were examined using multiple RT-PCR and Western-blot both at mRNA and protein level, respectively.
The current study confirmed the previous studies that ZEA could stimulate proliferation in MCF-7 cells with inducing a profound increase in S phase and a modest increase in G(2)/M phase that was accompanied by a decrease in G(0)/G(1) phase. ZEA could inhibit apoptosis in MCF-7 cells following estrogen ablation at a range of concentrations of 2 nmol/L -96 nmol/L. Western blot and RT-PCR analysis revealed that the anti-apoptotic bcl-2 was upregulated at both protein and mRNA level, together with the downregulation of pro-apoptotic bax.
ZEA should have possessed comparative estrogenic activity and could promote the progression of MCF-7 cells through the cell cycle by a decreasing in the G(0)/G(1) phase and by a significant increasing in S-phase. The pro-proliferative activity of ZEA was due to inhibition of apoptosis through regulation of bax/bcl-2 expression.
探讨玉米赤霉烯酮(ZEA)对雌激素依赖的人乳腺癌MCF-7细胞增殖和凋亡的影响及其潜在分子机制。
采用MTT法检测细胞活力,流式细胞术检测细胞周期分布。分别用细胞死亡检测ELISA法和流式细胞术检测细胞凋亡。分别采用多重RT-PCR和Western-blot法检测bax和bcl-2在mRNA和蛋白水平的表达。
本研究证实了先前的研究结果,即ZEA可刺激MCF-7细胞增殖,使S期显著增加,G(2)/M期适度增加,同时G(0)/G(1)期减少。在2 nmol/L - 96 nmol/L的一系列浓度下,ZEA可抑制雌激素去除后的MCF-7细胞凋亡。Western blot和RT-PCR分析显示,抗凋亡蛋白bcl-2在蛋白和mRNA水平均上调,同时促凋亡蛋白bax下调。
ZEA应具有相对雌激素活性,可通过减少G(0)/G(1)期和显著增加S期促进MCF-7细胞通过细胞周期进程。ZEA的促增殖活性是通过调节bax/bcl-2表达抑制细胞凋亡所致。