作者
Yue Bi, Ioannis I Verginadis, Souvik Dey, Lilie Lin, Linlang Guo, Yanfang Zheng, Constantinos Koumenis
发表日期
2018/9/1
期刊
Gynecologic oncology
卷号
150
期号
3
页码范围
534-544
出版商
Academic Press
简介
Objective
Approximately 15–25% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1/2 mutations. Inhibition of Poly (ADP-ribose) polymerase (PARP) is synthetically lethal to cells and tumors with BRCA1/2 mutation. Our goal was to investigate the radiosensitizing effects of PARP inhibitor olaparib in HGSOC with different BRCA1 status.
Methods
The radiosensitizing effects of olaparib were tested on BRCA1-proficient and deficient HGSOC by clonogenic survival and tumor growth assays. The effects of olaparib and radiation on DNA damage, PARP activity, and apoptosis were determined.
Results
BRCA1-deficient HGSOC cells were more sensitive to RT alone and exhibited significantly higher levels of olaparib-mediated radiosensitization compared to BRCA1-proficient cells. Furthermore, when combined with RT, olaparib inhibited DNA damage repair and PARP1 activity, increased apoptosis …
引用总数
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