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image of Overexpression of HNF4G can Increase the Resistance of Ovarian Cancer Cells to Olaparib

Abstract

Introduction

Ovarian cancer (OV) is one of the most malignant gynecological cancers. Poly(ADP-ribose) polymerase inhibitors (PARPi) represent the first-line maintenance therapy, effectively prolonging patient survival; however, the development of PARPi resistance poses a significant challenge for OV maintenance therapy. Previous studies have indicated that HNF4G functions as an oncogene in various tumors, but its role in OV development and Olaparib resistance remains unexplored.

Methods

We established an Olaparib-resistant OV cell line, SKOV3-PARPi, from the parental SKOV3 cell line. The impact of HNF4G on SKOV3 cell resistance to Olaparib was investigated using qRT-PCR, CCK-8 assay, Transwell assay, colony formation assay, scratch assay, Western blot, flow cytometry, as well as a nude mouse xenograft tumor model and immunohistochemistry. The function of HNF4G in SKOV3-Olaparib resistant cells was elucidated and subsequently validated through the animal tumor model.

Results

Prolonged Olaparib exposure induced acquired resistance in SKOV3 cells. Compared to parental OV cells, HNF4G expression was upregulated in Olaparib-resistant cells. Overexpression of HNF4G enhanced Olaparib resistance in OV cells, whereas HNF4G knockdown diminished it. Furthermore, increased protein levels of components within the PI3K-AKT signaling pathway were observed in Olaparib-resistant cells. Knocking down HNF4G expression in resistant cells significantly slowed tumor growth under Olaparib treatment. Changes in the protein levels of HNF4G and PI3K-AKT pathway components in the in vivo xenograft tumor tissues were consistent with the cellular observations.

Conclusion

Overexpression of HNF4G plays a crucial role in conferring Olaparib resistance in OV by activating the PI3K-AKT signaling pathway. HNF4G may serve as a potential therapeutic target for patients with Olaparib-resistant OV.

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2025-10-17
2025-11-08

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/content/journals/ccdt/10.2174/0115680096410121250926110350
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Overexpression of HNF4G can Increase the Resistance of Ovarian Cancer Cells to Olaparib
Bentham Science Publishers ; https://doi.org/10.2174/0115680096410121250926110350
/content/journals/ccdt/10.2174/0115680096410121250926110350
/content/journals/ccdt/10.2174/0115680096410121250926110350
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  • Article Type:     Research Article
Keywords: PI3K-AKT ; HNF4G ; Poly (ADP-ribose) polymerase inhibitors (PARPi) ; Resistance ; Ovarian cancer

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