Gao Yan-Hui, Zhang Hao-Peng, Yang Shu-Meng, Yang Yue, Ma Yu-Yan, Zhang Xin-Yu, Yang Yan-Mei
The Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Oncol Rep. 2014 Apr;31(4):1645-52. doi: 10.3892/or.2014.2994. Epub 2014 Jan 24.
Arsenic trioxide (As2O3) has been recognized as a potential chemotherapeutic agent, yet the details concerning its mechanism of action in solid cancers remain undetermined. The present study assessed the role of Akt in the cell death induced by As2O3. The MTT assay showed that As2O3 suppressed the proliferation of SGC-7901 cells in a dose- and time-dependent manner. Characteristic apoptotic changes were observed in the As2O3‑treated cells by Hoechst 33342 staining, and FACS analysis showed that As2O3 caused dose-dependent apoptotic cell death. As2O3 activated caspase-3 and -9, and PARP cleavage in a dose-dependent manner. Compromised mitochondrial membrane potential and an increased protein level of Bax indicated involvement of mitochondia. As2O3 decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that As2O3 inactivated Akt kinase. In addition, LY294002 (a PI3 kinase inhibitor) augmented the apoptosis induced by As2O3. These results demonstrated that inhibition of PI3K/Akt signaling was involved in As2O3-induced apoptosis of gastric cancer SGC-7901 cells.
三氧化二砷（As2O3）已被公认为一种潜在的化疗药物，但其在实体癌中的作用机制细节仍未明确。本研究评估了Akt在三氧化二砷诱导的细胞死亡中的作用。MTT分析表明，三氧化二砷以剂量和时间依赖性方式抑制SGC-7901细胞的增殖。通过Hoechst 33342染色在经三氧化二砷处理的细胞中观察到特征性凋亡变化，流式细胞术分析表明三氧化二砷导致剂量依赖性凋亡细胞死亡。三氧化二砷以剂量依赖性方式激活caspase-3和-9，并切割PARP。线粒体膜电位受损和Bax蛋白水平升高表明线粒体参与其中。三氧化二砷降低了p-Akt（Ser473）、p-Akt（Thr308）和p-GSK-3β（Ser9）的水平，表明三氧化二砷使Akt激酶失活。此外，LY294002（一种PI3激酶抑制剂）增强了三氧化二砷诱导的凋亡。这些结果表明，PI3K/Akt信号通路的抑制参与了三氧化二砷诱导的胃癌SGC-7901细胞凋亡。
