PGC1α promotes cisplatin resistance in human ovarian carcinoma cells through upregulation of mitochondrial biogenesis

International Journal of Oncology
Luyan ShenLian-Kun Sun

Abstract

The induction of lesions in nuclear and mitochondrial DNA by cisplatin is only a small component of its cytostatic/cytotoxic activity. The signaling pathway network in the nucleus and cytoplasm may contribute to chemotherapeutic resistance. Peroxisome proliferator-activated receptor-coactivator 1α (PGC1α)-mediated mitochondrial biogenesis regulates mitochondrial structural and the functional adaptive response against chemotherapeutic stress, and may be a therapeutic target. However, this regulatory network is complex and depends upon tumor types and environments, which require further investigation. Our previous study found that cisplatin-resistant ovarian epithelial carcinoma was more dependent on mitochondrial aerobic oxidation to support their growth, suggesting the association between mitochondrial function and chemotherapeutic resistance. In the present study, it was demonstrated that the expression of PGC1α and level of mitochondrial biogenesis were higher in cisplatin-resistant SKOV3/DDP cells compared with cisplatin-sensitive SKOV3 cells. Furthermore, SKOV3/DDP cells upregulated the expression of PGC1α and maintained mitochondrial structural and functional integrity through mitochondrial biogenesis under cisplatin stres...Continue Reading

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Citations

Apr 13, 2020·Journal of Cellular and Molecular Medicine·Lucia-Doina Popov
Apr 2, 2020·Frontiers in Pharmacology·Debora GrassoPierre Sonveaux
Apr 4, 2021·International Journal of Molecular Sciences·Yanqing LiLiankun Sun
Jun 3, 2021·International Journal of Molecular Sciences·Stine F PedersenLuis A Pardo

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