Mechanistic Study on Targeting Ferroptosis Regulates the Sensitivity of Ovarian Cancer Cells to PARP Inhibitors

CAI Li; YANG Yinhe; ZHAGN Xiu; LI Bei4; LIU Xiaoting; WU Nayiyuan

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Journal of Hunan Normal University(Medical Science) ›› 2024, Vol. 21 ›› Issue (6) : 5-10.

Basic Medicine

Mechanistic Study on Targeting Ferroptosis Regulates the Sensitivity of Ovarian Cancer Cells to PARP Inhibitors

CAI Li¹, YANG Yinhe¹, ZHAGN Xiu², LI Bei⁴, LIU Xiaoting³, WU Nayiyuan²

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Abstract

Objective Poly (ADP-ribose) polymerase (PARP) inhibitors have become an important means of maintenance therapy for ovarian cancer, significantly extending patients' survival periods. However, as treatment progresses, some patients gradually develop resistance to PARP inhibitors, which limits their clinical application. Enhancing the sensitivity of ovarian cancer patients to PARP inhibitors and delaying resistance are urgent issues to be addressed in the clinic. Recent studies have shown that targeting ferroptosis can increase the sensitivity of ovarian cancer cells to PARP inhibitors, with the underlying mechanisms requiring further investigation. Methods This study utilized bioinformatics analysis and pharmacological prediction models to select genes related to the ferroptosis pathway that are associated with PARP inhibitors in ovarian cancer. After knocking down the relevant genes, we assessed the IC50 of the PARP inhibitor niraparib in ovarian cancer cells. Results Bioinformatics and drug prediction analyses identified ferroptosis-related genes CSF-1R and SLCO2B1 as being associated with ovarian cancer PARP inhibitor sensitivity and significantly correlated with patient prognosis. Knockdown of CSF-1R and SLCO2B1 affected the sensitivity of ovarian cancer cells to the PARP inhibitor niraparib. Conclusion Targeting ferroptosis-related genes CSF-1R and SLCO2B1 can enhance the sensitivity of ovarian cancer cells to PARP inhibitors. This study provides new strategies for expanding the indications of PARP inhibitors in the clinic, overcoming resistance, and offers new evidence for combination therapy regimens involving PARP inhibitors.

Key words

ovarian cancer / PARP inhibitors / ferroptosis / CSF-1R / SLCO2B1

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CAI Li, YANG Yinhe, ZHAGN Xiu, LI Bei4, LIU Xiaoting, WU Nayiyuan. Mechanistic Study on Targeting Ferroptosis Regulates the Sensitivity of Ovarian Cancer Cells to PARP Inhibitors[J]. Journal of Hunan Normal University(Medical Science). 2024, 21(6): 5-10

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