GADD45[alpha] alleviates the CDDP resistance of SK-OV3/cddp cells via redox-mediated DNA damage

Epithelial ovarian cancer has the highest mortality rate of all malignant ovarian cancer types. Great progress has been made in the treatment of ovarian cancer in recent years. However, drug resistance has led to a low level of 5-year survival rate of epithelial ovarian cancer, and the molecular mec...

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Bibliographic Details
Published in:Oncology letters 2021-10, Vol.22 (4), p.1
Main Authors: Zhang, Qi-Zhu, Wen, Fang, Yang, Han-Lin, Cao, Yan-Yan, Peng, Ren Guo, Wang, Yuan-Mei, Nie, Lei, Qin, Yuan-Kun, Wu, Jin-Jian, Zhao, Xing, Zi, Dan
Format: Article
Language:English
Subjects:
Cancer
Care and treatment
DNA
DNA damage
Drug resistance
Health aspects
Ovarian cancer
Scientific equipment and supplies industry
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Summary:Epithelial ovarian cancer has the highest mortality rate of all malignant ovarian cancer types. Great progress has been made in the treatment of ovarian cancer in recent years. However, drug resistance has led to a low level of 5-year survival rate of epithelial ovarian cancer, and the molecular mechanism of which remains unknown. The aim of the present study was to identify the role of redox status in the cisplatin (CDDP) resistance of ovarian cancer. CDDP-resistant SK-OV3 (SK-OV3/cddp) cells were prepared and their reactive oxygen species and glutathione levels were investigated. The effects of hydrogen peroxide on the CDDP sensitivity of the SK-OV3/cddp cells and their expression levels of the redox-associated protein growth arrest and DNA damage 45a (GADD45[alpha]) were also investigated. In addition, the impact of GADD45[alpha] overexpression on cell viability was evaluated in vitro and in vivo, and the levels of Ser-139 phosphorylated H2A histone family member X ([gamma]-H2AX), which is associated with DNA damage, were detected. The results suggested that redox status affected the drug resistance of the ovarian cancer cells by increasing the expression of GADD45[alpha]. The overexpression of GADD45[alpha] reversed the CDDP resistance of the SK-OV3/cddp cells and increased the level of [gamma]-H2AX. In conclusion, GADD45[alpha] alleviated the CDDP resistance of SK-OV3/cddp cells via the induction of redox-mediated DNA damage. Key words: cisplatin resistance, SK-OV3 cells, redox, growth arrest and DNA damage 45a, DNA damage
ISSN:1792-1074
DOI:10.3892/ol.2021.12981