Huang Han-Ming, Huang Xiao-Yu, Wu Shao-Ping, Chen Can-Keng, He Xin-Hua, Zhang Yong-Fa
Department of Anesthesiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People's Republic of China.
Department of Physiology, Shantou University Medical College, Shantou, 515041, People's Republic of China.
Cell Mol Biol Lett. 2022 Mar 19;27(1):28. doi: 10.1186/s11658-022-00324-w.
Parecoxib plays an important role in inhibition of human cancer. However, the effect of parecoxib on esophageal squamous cell carcinoma (ESCC) is still not well known. The purpose of this study was to investigate the effect of parecoxib on ESCC and its underlying mechanism.
RNA-sequence analysis was performed to identify functional alterations and mechanisms. Cell cycle, proliferation, invasion, and migration were assessed using flow cytometry, CCK-8 assay, colony formation, transwell, and wound healing assays. Extracellular matrix (ECM) degradation was detected by substrate gel zymography and 3D cell culture assay. Western blotting was used to detect parecoxib-dependent mechanisms involving cell cycle, proliferation, invasion, and migration. Tumor formation in vivo was detected by mouse assay.
Functional experiments indicated that parecoxib induced ESCC cell cycle arrest in G2 phase, and inhibited cell proliferation, invasion, and migration in vitro. Western blotting revealed that parecoxib downregulated the phosphorylation levels of AKT and PDK1, as well as the expression of the mutant p53, cyclin B1, and CDK1, while upregulating p21waf1. Parecoxib inhibited matrix metalloproteinase-2 (MMP2) secretion and invadopodia formation, which were related to ECM degradation. Furthermore, we found that parecoxib suppressed ESCC growth in heterotopic tumor models.
Parecoxib inhibits ESCC progression, including cell cycle, proliferation, invasion, and migration, via the PDK1-AKT signaling pathway.
帕瑞昔布在抑制人类癌症方面发挥着重要作用。然而，帕瑞昔布对食管鳞状细胞癌（ESCC）的影响仍不为人所知。本研究的目的是探讨帕瑞昔布对ESCC的影响及其潜在机制。
进行RNA序列分析以确定功能改变和机制。使用流式细胞术、CCK-8检测、集落形成、Transwell和伤口愈合检测来评估细胞周期、增殖、侵袭和迁移。通过底物凝胶酶谱法和3D细胞培养检测来检测细胞外基质（ECM）降解。使用蛋白质印迹法检测涉及细胞周期、增殖、侵袭和迁移的帕瑞昔布依赖性机制。通过小鼠实验检测体内肿瘤形成。
功能实验表明，帕瑞昔布诱导ESCC细胞周期停滞在G2期，并在体外抑制细胞增殖、侵袭和迁移。蛋白质印迹显示，帕瑞昔布下调AKT和PDK1的磷酸化水平，以及突变型p53、细胞周期蛋白B1和CDK1的表达，同时上调p21waf1。帕瑞昔布抑制与ECM降解相关的基质金属蛋白酶-2（MMP2）分泌和侵袭伪足形成。此外，我们发现帕瑞昔布在异位肿瘤模型中抑制ESCC生长。
帕瑞昔布通过PDK1-AKT信号通路抑制ESCC进展，包括细胞周期、增殖、侵袭和迁移。
