Xu Qian, Jia Xiyun, Wu Qian, Shi Lei, Ma Zihan, Ba Nan, Zhao Han, Xia Xingzhou, Zhang Zisen
Department of Oncology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Gastroenterology, Huanghe Central Hospital, Zhengzhou, Henan 450003, P.R. China.
Oncol Lett. 2020 Dec;20(6):329. doi: 10.3892/ol.2020.12193. Epub 2020 Oct 6.
Recently, proton pump inhibitors have become a hot research topic in the field of cancer drug research. However, the specific anti-tumor effect and underlying mechanisms of esomeprazole (ESO) in gastric cancer (GC) have remained elusive. In the present study, the toxic effects of ESO on the GC cell line AGS were investigated. MTT assays confirmed that ESO inhibited the proliferation of AGS cells and significantly enhanced their chemosensitivity. Transwell assays were performed to determine the anti-metastatic effects of ESO in AGS cells. Flow cytometry demonstrated that ESO induced cell apoptosis and caused cell cycle arrest in the S and G2/M phases. Furthermore, the differential expression of 948 long non-coding RNAs (lncRNAs), 114 circular RNAs (circRNAs), 1,197 mRNAs and 199 microRNAs (miRNAs) was detected in AGS cells via microarray analysis and RNA-sequencing. The top 10 differently expressed genes were mostly located on chromosomes 10 and 19. In addition, Gene Ontology analysis indicated that the genes were accumulated in functional terms associated with DNA replication, the cell cycle and the apoptotic signaling pathway. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed a variety of significantly dysregulated signaling pathways and targets, including the EGFR tyrosine kinase inhibitor resistance pathway, forkhead box O signaling pathway, p53 signaling pathway and platinum drug resistance pathway. Subsequently, the interactions of microtubule-associated protein 2 (MAP2), homeodomain-interacting protein kinase 2 (HIPK2) and ankyrin 2 (ANK2) were noted in a competing endogenous RNA (ceRNA) network, which may be important targets of ESO, exerting an anti-tumor effect in AGS cells. Collectively, ESO affects the proliferation, metastasis, apoptosis and chemosensitivity of gastric cancer cells by regulating long non-coding RNA/circRNA-miRNA-mRNA ceRNA networks.
最近，质子泵抑制剂已成为癌症药物研究领域的一个热门研究课题。然而，埃索美拉唑（ESO）在胃癌（GC）中的具体抗肿瘤作用及潜在机制仍不清楚。在本研究中，研究了ESO对胃癌细胞系AGS的毒性作用。MTT分析证实ESO抑制AGS细胞的增殖并显著增强其化学敏感性。进行Transwell分析以确定ESO对AGS细胞的抗转移作用。流式细胞术表明ESO诱导细胞凋亡并导致细胞周期停滞在S期和G2/M期。此外，通过微阵列分析和RNA测序在AGS细胞中检测到948个长链非编码RNA（lncRNA）、114个环状RNA（circRNA）、1197个信使RNA（mRNA）和199个微小RNA（miRNA）的差异表达。前10个差异表达基因大多位于10号和19号染色体上。此外，基因本体分析表明这些基因在与DNA复制、细胞周期和凋亡信号通路相关的功能术语中积累。京都基因与基因组百科全书通路分析揭示了多种显著失调的信号通路和靶点，包括表皮生长因子受体酪氨酸激酶抑制剂耐药通路、叉头框O信号通路、p53信号通路和铂类药物耐药通路。随后，在竞争性内源性RNA（ceRNA）网络中发现了微管相关蛋白2（MAP2）、同源结构域相互作用蛋白激酶2（HIPK2）和锚蛋白2（ANK2）的相互作用，这可能是ESO的重要靶点，在AGS细胞中发挥抗肿瘤作用。总体而言，ESO通过调节长链非编码RNA/circRNA-miRNA-mRNA ceRNA网络影响胃癌细胞的增殖、转移、凋亡和化学敏感性。
