Department of Pharmacy, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
J Cancer Res Ther. 2022 Apr;18(2):362-369. doi: 10.4103/jcrt.jcrt_968_21.
This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin.
HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin.
Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells.
PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy.
本研究旨在探讨泮托拉唑（PPZ）对宫颈癌（CC）细胞对顺铂敏感性的影响。
将 HeLa 和 CaSki 细胞暴露于顺铂和/或 PPZ 处理中。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）比色法、集落形成实验、流式细胞术、划痕愈合实验和 Transwell 实验分别检测 CC 细胞的活力、增殖、凋亡、迁移和侵袭。然后，通过蛋白质印迹法测量 Beclin-1、LC3 和 p62 的表达。雷帕霉素（Rapa）作为自噬激活剂，用于证实自噬对 CC 细胞对顺铂敏感性的影响。
顺铂处理抑制 CC 细胞活力和增殖并加速细胞凋亡。顺铂与 PPZ 联合或单独使用均可显著抑制 CC 细胞活力、增殖、迁移和侵袭，并增加细胞凋亡。顺铂增强了 Beclin1 和 LC3II/I 的表达水平，降低了 p62 的表达。顺铂与 PPZ 联合使用可显著降低 Beclin1 和 LC3II/I 的表达水平，但增加了 p62 的表达。自噬激活剂 Rapa 消除了顺铂与 PPZ 联合使用对自噬的抑制作用，并增强了 CC 细胞的活力，但抑制了细胞凋亡。
PPZ 通过抑制顺铂诱导的细胞自噬来提高 CC 细胞对顺铂的敏感性。
