Najafi Dena, Siri Goli, Sadri Maryam, Yazdani Omid, Esbati Romina, Karimi Parvin, Keshavarz Ali, Mehmandar-Oskuie Amirreza, Ilktac Mehmet
Faculty of Pharmacy, Eastern Mediterranean University, Famagusta, North Cyprus, Turkey.
Department of Internal Medicine, Amir Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Biotechnol Appl Biochem. 2024 Aug;71(4):809-816. doi: 10.1002/bab.2578. Epub 2024 Mar 18.
Gastric cancer (GC) is a prominent cause of cancer-related mortality worldwide. Long noncoding RNA (lncRNA) maternal expression gene3 (MEG3) participates in numerous signaling pathways by targeting the miRNA-mRNA axis. Studies on human tumors have demonstrated that the antibiotic Ciprofloxacin induces cell cycle changes, programmed cell death, and growth suppression. In this study, we transfected MEG3 lncRNA and Ciprofloxacin into the MKN-45 GC cell line. qRT-PCR was employed to evaluate the effects on the specific microRNA and mRNA. The wound healing test, MTT assay, and flow cytometry were used to assess the impact of their administration on cell migration, viability, and apoptosis, respectively. Research showed that miR-147 expression fell even more after MEG3 lncRNA transfection, leading to an increase in B-cell lymphoma 2 (BCL-2) levels. Ciprofloxacin transfection did not significantly affect the axis, except for MEG3, which led to its slight upregulation. MEG3 lncRNA inhibited the migration of MKN-45 cells compared to the control group. When MEG3 lncRNA was coupled with Ciprofloxacin, there was a significant reduction in cell migration compared to untreated groups and controls. MTT assay and flow cytometry demonstrated that MEG3 lncRNA decreased cell viability and triggered apoptosis. Simultaneous administration of MEG3 lncRNA and Ciprofloxacin revealed a significant reduction in cell viability caused by increased apoptosis obtained from MTT or flow cytometry assays. Modulating the miR-147-BCL-2 axis decreases cell migration and survival while promoting cell death. In conclusion, combining MEG3 lncRNA with Ciprofloxacin may be an effective therapeutic approach for GC treatment by influencing the miR-14-BCl-2 axis, resulting in reduced cell viability, migration, and increased apoptosis.
胃癌（GC）是全球癌症相关死亡的一个主要原因。长链非编码RNA（lncRNA）母系表达基因3（MEG3）通过靶向miRNA-mRNA轴参与众多信号通路。对人类肿瘤的研究表明，抗生素环丙沙星可诱导细胞周期变化、程序性细胞死亡和生长抑制。在本研究中，我们将MEG3 lncRNA和环丙沙星转染到MKN-45胃癌细胞系中。采用qRT-PCR评估对特定微小RNA和信使核糖核酸的影响。伤口愈合试验、MTT法和流式细胞术分别用于评估它们的给药对细胞迁移、活力和凋亡的影响。研究表明，MEG3 lncRNA转染后miR-147表达进一步下降，导致B细胞淋巴瘤2（BCL-2）水平升高。环丙沙星转染除导致MEG3轻微上调外，对该轴无显著影响。与对照组相比，MEG3 lncRNA抑制了MKN-45细胞的迁移。当MEG3 lncRNA与环丙沙星联合使用时，与未处理组和对照组相比，细胞迁移显著减少。MTT法和流式细胞术表明，MEG3 lncRNA降低了细胞活力并引发了凋亡。同时给予MEG3 lncRNA和环丙沙星显示，MTT或流式细胞术检测显示，由于凋亡增加，细胞活力显著降低。调节miR-147-BCL-2轴可减少细胞迁移和存活，同时促进细胞死亡。总之，将MEG3 lncRNA与环丙沙星联合使用可能是一种有效的胃癌治疗方法，通过影响miR-14-BCl-2轴，导致细胞活力降低、迁移减少和凋亡增加。
