Duan Jingya, Zhang Zisen, Du Jinfeng, Zhang Jihua, Li Minmin, Li Canyu
Department of Gynecology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
Department of Oncology, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People's Republic of China.
Onco Targets Ther. 2023 Jun 20;16:425-440. doi: 10.2147/OTT.S406009. eCollection 2023.
Ovarian cancer is the most lethal malignancy in gynecology. Due to limited treatment strategies and platinum resistance, newer drugs and therapeutic options are needed. Esomeprazole (ESO) has been reported to have multiple anticancer activities in preclinical and clinical research. Therefore, this study aimed to explore the anticancer effects of esomeprazole on ovarian cancer and its underlying molecular mechanisms.
CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell viability and proliferation. The Transwell assay was used to evaluate cell migration and invasion capacity. Flow cytometry was used to detect cell apoptosis. Western blotting and immunofluorescence were used to detect protein expression.
ESO effectively inhibited the cell viability, proliferation, invasion, migration, and induced apoptosis of ovarian cancer cells in a concentration-dependent manner. Treatment with ESO decreased the expression of c-MYC, SKP2, E2F1, N-cadherin, vimentin, and matrix metalloproteinase 2 (MMP2), while it increased E-cadherin, caspase3, p53, BAX, and cleaved poly (ADP-ribose) polymerase (PARP) expression, and downregulated the PI3K/AKT/mTOR signaling pathway. Furthermore, ESO combined with cisplatin showed synergistic effects in inhibiting proliferation, invasion, and migration of cisplatin-resistant ovarian cancer cells. The mechanism may be related to the increased inhibition of c-MYC, epithelial-mesenchymal transition (EMT), and the AKT/mTOR signaling pathway and enhanced the upregulation of the pro-apoptotic protein BAX and cleaved PARP levels. Moreover, ESO combined with cisplatin synergistically upregulated the expression of the DNA damage marker γH2A.X.
ESO exerts multiple anticancer activities and has a synergistic effect in combination with cisplatin on cisplatin-resistant ovarian cancer cells. This study provides a promising strategy to improve chemosensitivity and overcome resistance to cisplatin in ovarian cancer.
卵巢癌是妇科最致命的恶性肿瘤。由于治疗策略有限以及铂耐药性问题，需要更新的药物和治疗选择。在临床前和临床研究中，埃索美拉唑（ESO）已被报道具有多种抗癌活性。因此，本研究旨在探讨埃索美拉唑对卵巢癌的抗癌作用及其潜在的分子机制。
采用CCK-8和5-乙炔基-2'-脱氧尿苷（EdU）检测法检测细胞活力和增殖情况。采用Transwell检测法评估细胞迁移和侵袭能力。采用流式细胞术检测细胞凋亡。采用蛋白质免疫印迹法和免疫荧光法检测蛋白质表达。
ESO以浓度依赖性方式有效抑制卵巢癌细胞的活力、增殖、侵袭、迁移，并诱导其凋亡。ESO处理降低了c-MYC、SKP2、E2F1、N-钙黏蛋白、波形蛋白和基质金属蛋白酶2（MMP2）的表达，同时增加了E-钙黏蛋白、半胱天冬酶3、p53、BAX和裂解的聚（ADP-核糖）聚合酶（PARP）的表达，并下调了PI3K/AKT/mTOR信号通路。此外，ESO与顺铂联合使用在抑制顺铂耐药卵巢癌细胞的增殖、侵袭和迁移方面显示出协同作用。其机制可能与增强对c-MYC、上皮-间质转化（EMT）和AKT/mTOR信号通路的抑制作用以及增强促凋亡蛋白BAX和裂解的PARP水平的上调有关。此外，ESO与顺铂联合使用可协同上调DNA损伤标志物γH2A.X的表达。
ESO发挥多种抗癌活性，与顺铂联合使用对顺铂耐药卵巢癌细胞具有协同作用。本研究为提高卵巢癌的化疗敏感性和克服顺铂耐药性提供了一种有前景的策略。
