PHGDH Inhibitor CBR-5884 Inhibits Epithelial Ovarian Cancer Progression via ROS/Wnt/β-Catenin Pathway and Plays a Synergistic Role with PARP Inhibitor Olaparib.
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| 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.
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| Authors | Xiaocui Zhang, Meige Sun, Yisheng Jiao, Bei Lin, Qing Yang |
| Journal | Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 9029544 ( 2022) ISSN: 1942-0994 [Electronic] United States |
| PMID | 36105480 (Publication Type: Journal Article) |
| Copyright | Copyright © 2022 Xiaocui Zhang et al. |
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