Qiao Juan, Wang Wei-Jing, Zhang Yuan
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Gynecology Department Five of The Harbin Red Cross Center Hospital, Harbin, Heilongjiang 150076, P.R. China.
Oncol Lett. 2018 Nov;16(5):6417-6422. doi: 10.3892/ol.2018.9460. Epub 2018 Sep 19.
Aclidinium, a muscarinic antagonist, is generally used to treat the respiratory system diseases whereas it is not clear whether aclidinium has therapeutic effect in ovarian cancer (OC). The aim of this study was to investigate the impact of aclidinium on OC and its potential mechanism. CCK-8 was employed to test the potential effect of aclidinium on SKOV3 cell proliferation. Transwell migration and invasion assay was performed to assess the influence of aclidinium on SKOV3 cell metastasis and invasion. Furthermore, flow cytometry apoptotic analysis was used to evaluate the effect of aclidinium on cell apoptosis. Finally, western blotting was applied to determine the changes of key proteins in apoptosis and PI3K/AKT/mTOR signaling pathway induced by aclidinium. The study showed that aclidinium had antiproliferative activity on SKOV3 cells. Simultaneously, aclidinium could significantly inhibit the number of migrated and invaded SKOV3 cells and markedly increased the SKOV3 cell apoptosis rate. Mechanistically, the expression of PI3K/AKT/mTOR signaling pathway related proteins were significantly inhibited in aclidinium treated SKOV3 cells. Our findings proposed a clue for further OC studies in preclinical and clinical treatment and aclidinium may be useful for the treatment of OC in the future.
阿地溴铵是一种毒蕈碱拮抗剂,通常用于治疗呼吸系统疾病,然而阿地溴铵对卵巢癌(OC)是否具有治疗作用尚不清楚。本研究的目的是探讨阿地溴铵对OC的影响及其潜在机制。采用CCK-8检测阿地溴铵对SKOV3细胞增殖的潜在作用。进行Transwell迁移和侵袭试验以评估阿地溴铵对SKOV3细胞转移和侵袭的影响。此外,采用流式细胞术凋亡分析评估阿地溴铵对细胞凋亡的作用。最后,应用蛋白质免疫印迹法测定阿地溴铵诱导的凋亡及PI3K/AKT/mTOR信号通路关键蛋白的变化。研究表明,阿地溴铵对SKOV3细胞具有抗增殖活性。同时,阿地溴铵可显著抑制SKOV3细胞的迁移和侵袭数量,并显著提高SKOV3细胞凋亡率。机制上,在阿地溴铵处理的SKOV3细胞中,PI3K/AKT/mTOR信号通路相关蛋白的表达受到显著抑制。我们的研究结果为OC的临床前和临床治疗的进一步研究提供了线索,阿地溴铵未来可能对OC的治疗有用。