Wang Ying, Zhang Yong, Yang Lei, Cai Benzhi, Li Jianping, Zhou You, Yin Li, Yang Lili, Yang Bao Feng, Lu Yan Jie
Department of Pharmacology, State-Province Key Laboratories of Biomedicine and Pharmaceutics, and.
Exp Ther Med. 2011 May;2(3):481-486. doi: 10.3892/etm.2011.224. Epub 2011 Mar 8.
Arsenic trioxide (As(2)O(3)) has been widely used to treat patients with acute promyelocytic leukemia and has also been shown to exhibit therapeutic effects on various types of solid tumors, including gastric cancer and lung carcinoma. Breast cancer is a type of solid tumor whose incidence has been increasing for many years. The present study was designed to investigate the effects of As(2)O(3) on the human breast cancer cell line MCF-7, and to explore its potential mechanisms. The MTT assay demonstrated that As(2)O(3) decreased the cellular viability of MCF-7 cells in a concentration-dependent manner. Morphological observation, the TUNEL assay and flow cytometric analysis revealed that apoptosis was involved in the process. An assay for caspase-3 activity suggested that the apoptosis was mediated through caspase-3 activation. Further investigation indicated that protein levels of the human ether-a-go-go-related gene (HERG) were markedly downregulated by As(2)O(3). Taken together, the results indicate that arsenic trioxide induces the apoptosis of human breast cancer MCF-7 cells at least in part through the activation of caspase-3 and the decrease in HERG expression.
三氧化二砷（As₂O₃）已被广泛用于治疗急性早幼粒细胞白血病患者，并且也已显示出对包括胃癌和肺癌在内的各种实体瘤具有治疗作用。乳腺癌是一种实体瘤，其发病率多年来一直在上升。本研究旨在探讨As₂O₃对人乳腺癌细胞系MCF-7的影响，并探索其潜在机制。MTT法表明，As₂O₃以浓度依赖性方式降低MCF-7细胞的细胞活力。形态学观察、TUNEL检测和流式细胞术分析表明，该过程涉及细胞凋亡。caspase-3活性检测表明，细胞凋亡是通过caspase-3激活介导的。进一步研究表明，As₂O₃可显著下调人ether-a-go-go相关基因（HERG）的蛋白水平。综上所述，结果表明三氧化二砷至少部分通过激活caspase-3和降低HERG表达诱导人乳腺癌MCF-7细胞凋亡。
