PHGDH Inhibitor CBR‐5884 Inhibits Epithelial Ovarian Cancer Progression via ROS/Wnt/<i>β</i>‐Catenin Pathway and Plays a Synergistic Role with PARP Inhibitor Olaparib
Xiaocui Zhang, Meige Sun, Yisheng Jiao, Bei Lin, Qing Yang
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.