Cheng Baohua, Yang Xinxin, Han Zaiwen, An Liangxiang, Liu Shuwei
Shandong University, Jinan, China.
Auris Nasus Larynx. 2008 Mar;35(1):95-101. doi: 10.1016/j.anl.2007.07.009. Epub 2007 Sep 14.
Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumor cell lines, where induction of differentiation and apoptosis are the prime effects. As a novel anticancer agent for treatment of solid cancers, As(2)O(3) is promising and the mechanism has been not still fully understood. Laryngeal squamous cell carcinoma (LSCC) is one common tumor in head and neck cancers. The objective of this study was to investigate the effects of As(2)O(3) on LSCC cell line HEP-2, and their possible involvement in As(2)O(3)-induced apoptosis.
The cell viability was analyzed by MTT assay method and the morphological changes were observed by an inverted microscope and acridine orange (AO) staining. The caspase-3 activity was measured by a fluorophotometer. The expression of survivin mRNA was evaluated by RT-PCR.
In this study, we demonstrated an apoptotic effect of As(2)O(3) in LSCC cell line Hep-2. In Hep-2 cells, As(2)O(3) decreased the cell viability, inhibited the growth and proliferation, induced apoptosis and increased the activity of caspase-3 in a dose-dependent manner. And the expression of survivin mRNA was also decreased in a dose-dependent manner.
We concluded that As(2)O(3) induced the apoptosis of Hep-2 cells via down-regulating the expression of survivin mRNA.
三氧化二砷(As₂O₃)临床上用于治疗急性早幼粒细胞白血病,在体外对多种实体瘤细胞系具有活性,其主要作用是诱导分化和凋亡。作为一种治疗实体癌的新型抗癌药物,As₂O₃具有广阔前景,但其作用机制尚未完全明确。喉鳞状细胞癌(LSCC)是头颈部常见肿瘤之一。本研究旨在探讨As₂O₃对LSCC细胞系HEP - 2的影响及其可能参与As₂O₃诱导凋亡的机制。
采用MTT法分析细胞活力,通过倒置显微镜和吖啶橙(AO)染色观察细胞形态变化。用荧光光度计检测caspase - 3活性。通过RT - PCR评估survivin mRNA的表达。
在本研究中,我们证实了As₂O₃对LSCC细胞系Hep - 2具有凋亡作用。在Hep - 2细胞中,As₂O₃以剂量依赖性方式降低细胞活力、抑制生长和增殖、诱导凋亡并增加caspase - 3活性。survivin mRNA的表达也以剂量依赖性方式降低。
我们得出结论,As₂O₃通过下调survivin mRNA的表达诱导Hep - 2细胞凋亡。