Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
Biochem Biophys Res Commun. 2013 Jan 4;430(1):250-5. doi: 10.1016/j.bbrc.2012.10.143. Epub 2012 Nov 17.
DNA methyltransferase (DNMT) inhibitor zebularine has been reported to potentiate the anti-tumor effect by reactivating the expression of tumor suppressor genes and apoptosis-related genes in various malignant cells. However, the apoptotic signaling pathway in gastric cancer cells induced by zebularine is not well understood. In the study, the effects of zebularine on the growth and apoptosis of gastric cancer cells were investigated by MTT assay, Hoechst assay, Western blot analysis, flow cytometric analysis of annexin V-FITC/PI staining, and TUNEL assay. Zebularine was an effective inhibitor of human gastric cancer cells proliferation in vitro and in vivo. The effects were dose dependent. A zebularine concentration of 50 μM accounted for the inhibition of cell proliferation of 67% at 48 h. The treatment with zebularine upregulated Bax, and decreased Bcl-2 protein. Caspase-3 was activated, suggesting that the apoptosis is mediated by mitochondrial pathways. Moreover, zebularine injection successfully inhibited the tumor growth via apoptosis induction which was demonstrated by TUNEL assay in xenograft tumor mouse model. These results demonstrated that zebularine induced apoptosis in gastric cancer cells via mitochondrial pathways, and zebularine might become a therapeutic approach for the treatment of gastric cancer.
DNA 甲基转移酶（DNMT）抑制剂地西他滨已被报道通过重新激活各种恶性细胞中肿瘤抑制基因和凋亡相关基因的表达来增强抗肿瘤作用。然而，地西他滨诱导胃癌细胞凋亡的信号通路尚不清楚。在这项研究中，通过 MTT 检测、Hoechst 检测、Western blot 分析、流式细胞术检测 Annexin V-FITC/PI 染色和 TUNEL 检测，研究了地西他滨对胃癌细胞生长和凋亡的影响。地西他滨是体外和体内人胃癌细胞增殖的有效抑制剂。其作用呈剂量依赖性。地西他滨浓度为 50μM 时，在 48 小时时抑制细胞增殖 67%。地西他滨处理上调了 Bax，下调了 Bcl-2 蛋白。Caspase-3 被激活，表明凋亡是通过线粒体途径介导的。此外，地西他滨注射通过 TUNEL 检测在异种移植肿瘤小鼠模型中成功诱导了肿瘤细胞凋亡，从而成功抑制了肿瘤生长。这些结果表明，地西他滨通过线粒体途径诱导胃癌细胞凋亡，地西他滨可能成为治疗胃癌的一种方法。
