miR-21 inhibits the effects of cyclooxygenase-2 inhibitor NS398 on apoptosis and invasion in gastric cancer cells.
miR-21 inhibits the effects of cyclooxygenase-2 inhibitor NS398 on apoptosis and invasion in gastric cancer cells.
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DOI：
10.2147/ott.s90012
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发表时间：
2015
影响因子：
4
通讯作者：
Fan X
中科院分区：
文献类型：
--
作者：
Li H;Cheng J;Mao Y;Jiang M;Fan X
探讨 miR-21 在环氧合酶 2 抑制剂 NS398 诱导的胃癌 (GC) 细胞凋亡和侵袭中的作用。 AGS 细胞用 NS398 处理并用 miR-21 转染。使用定量实时聚合酶链反应来测量 miR-21 mRNA 表达。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记和流式细胞术分析来评估凋亡细胞。 Western blot检测Cleaved caspase-3、Bcl-2、Bax、Bak、PTEN蛋白表达。分别通过transwell和伤口愈合测定来测量侵袭和迁移的能力。用 NS398 处理 AGS 细胞以剂量依赖性方式诱导细胞凋亡，并伴随 miR-21 mRNA 表达的显着下调。通过将 miR-21 模拟物转染至 AGS 细胞来上调 miR-21 表达，从而阻断 NS398 诱导的细胞凋亡。用 NS398 处理 AGS 细胞会诱导 Bcl-2 蛋白家族成员发生变化，显示 Bax、Bak 和 PTEN 蛋白表达增加，同时 Bcl-2 蛋白表达减少。在转染 miR-21 模拟物的细胞中，这些变化被逆转。 NS398 诱导的细胞侵袭和迁移的减少被 miR-21 的上调所阻断。 miR-21 通过调节凋亡相关蛋白介导 NS398 在 GC 细胞中的抗癌作用。 miR-21是这种特异性环氧合酶2抑制剂预防和治疗GC的分子靶点之一。
To investigate the role of miR-21 in cyclooxygenase-2 inhibitor NS398-induced apoptosis and invasion in gastric cancer (GC) cells. AGS cells were treated with NS398 and transfected with miR-21. Quantitative real-time polymerase chain reaction was used to measure miR-21 mRNA expression. Apoptotic cells were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and flow cytometric analysis. The protein expression of cleaved caspase-3, Bcl-2, Bax, Bak, and PTEN was detected by Western blot. The capacities for invasion and migration were measured by transwell and wound-healing assays, respectively. Treatment of AGS cells with NS398 induced apoptosis in a dose-dependent manner accompanied by significant downregulation of miR-21 mRNA expression. Upregulation of miR-21 expression by transfection of miR-21 mimics into AGS cells blocked NS398-induced apoptosis. Treatment of AGS cells with NS398 induced changes in Bcl-2 protein family members, showing an increase in the protein expression of Bax, Bak, and PTEN, with a concomitant decrease in the protein expression of Bcl-2. In cells transfected with miR-21 mimics, these changes were reversed. The decrease in cellular invasiveness and migration induced by NS398 was blocked by upregulation of miR-21. miR-21 mediates anticancer effects of NS398 in GC cells by regulating apoptosis-related proteins. miR-21 is one of the molecular targets of this specific cyclooxygenase-2 inhibitor in the prevention and treatment of GC.