PHGDH Inhibitor CBR-5884 Inhibits Epithelial Ovarian Cancer Progression via ROS/Wnt/β-Catenin Pathway and Plays a Synergistic Role with PARP Inhibitor Olaparib. (5th September 2022)

• Record Type: Journal Article
• Authors: Zhang, Xiaocui; Sun, Meige; Jiao, Yisheng; Lin, Bei; Yang, Qing
• Other Names: Zhang Junmin Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2022(2022)
• Publication Date: 2022-09-05
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2022/9029544
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : PHGDH attaches importance to serine biosynthesis in cancer cells and maintaining mitochondrial redox homeostasis. However, the role of PHGDH inhibitor CBR-5884 in cell ROS level and its downstream pathways has not been explored in epithelial ovarian cancer. Thus, we investigated the function and possible mechanism of PHGDH inhibitor CBR-5884 on epithelial ovarian cancer in vitro and in vivo. A2780, OVCAR3, and ES-2 were treated with CBR-5884 at different concentrations or different time points. Results showed that CBR-5884 inhibited epithelial ovarian cancer cell proliferation, migration, and invasion and increases cell ROS level. Meanwhile, CBR-5884 exerts antitumor effect through activating ROS/Wnt/ β -catenin pathway. Besides, CBR-5884 exerts antitumor effect in vivo. What's more, we explored the effect of CBR-5884 with or without PARP inhibitor Olaparib, which showed that the two together had a larger effect. In conclusion, PHGDH inhibitor CBR-5884 inhibits epithelial ovarian cancer proliferation, migration, and invasion through activating ROS/Wnt/ β -catenin pathway and plays a synergistic role with PARP inhibitor olaparib, which provided a theoretical basis for PHGDH inhibitor CBR-5884 in clinical treatment.