Liu Xiao-hong, Zheng Xue-fang, Wang Yong-li
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
Chin Med J (Engl). 2009 Jul 20;122(14):1681-5.
Breast cancer is one of the most common malignancies in women and is highly resistant to chemotherapy. Due to its high tumour selectivity, 3-bromopyruvic acid (3-BrPA), a well-known inhibitor of energy metabolism has been proposed as a specific anticancer agent. The present study determined the effect of 3-BrPA on proliferation, cell cycle and apoptosis in the human breast cancer MCF-7 cell line and other antitumour mechanisms.
MCF-7 cells were treated with various concentrations of 3-BrPA for 1 - 4 days, and cell growth was measured by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay. Marked morphological changes in MCF-7 cells after treatment with 3-BrPA were observed using transmission electron microscopy. The distributions of the cell cycle and apoptosis were analyzed by flow cytometry. Immunohistochemistry was used to indicate the changes in the expression of Bcl-2, c-Myc, and mutant p53.
3-BrPA (25 microg/ml) significantly inhibited the proliferation of MCF-7 cells in a time-dependent manner. The MCF-7 cells exposed to 3-BrPA showed the typical morphological characteristics of apoptosis, including karyopycnosis, nuclear condensation and oversize cytoplasmic particles. In addition, flow cytometric assay also showed more apoptotic cells after 3-BrPA stimulation. The cells at the G0 and G1 phases were dramatically decreased while cells at the S and G2/M phases were increased in response to 3-BrPA treatment after 48 hours. Furthermore, 3-BrPA stimulation decreased the expressions of Bcl-2, c-Myc and mutant p53, which were strongly associated with the programmed cell death signal transduction pathway.
3-BrPA inhibits proliferation, induces S phase and G2/M phase arrest, and promotes apoptosis in MCF-7 cells, which processes might be mediated by the downregulation of the expressions of Bcl-2, c-Myc and mutant p53.
乳腺癌是女性最常见的恶性肿瘤之一，对化疗具有高度抗性。由于其高肿瘤选择性，3-溴丙酮酸（3-BrPA），一种著名的能量代谢抑制剂，已被提议作为一种特异性抗癌剂。本研究确定了3-BrPA对人乳腺癌MCF-7细胞系增殖、细胞周期和凋亡的影响以及其他抗肿瘤机制。
用不同浓度的3-BrPA处理MCF-7细胞1 - 4天，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑法测定细胞生长。用透射电子显微镜观察3-BrPA处理后MCF-7细胞明显的形态变化。通过流式细胞术分析细胞周期分布和凋亡情况。免疫组织化学用于指示Bcl-2、c-Myc和突变型p53表达的变化。
3-BrPA（25微克/毫升）以时间依赖性方式显著抑制MCF-7细胞的增殖。暴露于3-BrPA的MCF-7细胞表现出典型的凋亡形态特征，包括核固缩、核浓缩和超大的细胞质颗粒。此外，流式细胞术检测也显示3-BrPA刺激后凋亡细胞增多。48小时后，3-BrPA处理使G0期和G1期细胞显著减少，而S期和G2/M期细胞增加。此外，3-BrPA刺激降低了Bcl-2、c-Myc和突变型p53的表达，这些与程序性细胞死亡信号转导通路密切相关。
3-BrPA抑制MCF-7细胞的增殖，诱导S期和G2/M期阻滞，并促进其凋亡，这些过程可能是由Bcl-2、c-Myc和突变型p53表达下调介导的。
