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Olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer
- Source :
- Journal of Gynecologic Oncology
- Publication Year :
- 2019
- Publisher :
- Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy, 2019.
-
Abstract
- Objective Poly (ADP-ribose) polymerase (PARP) is an important molecule in the early stress response of DNA damage, which is involved in DNA damage repair and cellular senescence. Olaparib, as PARP inhibitor, has an anti-tumor effect on high grade serous ovarian cancer, but its effects on cellular senescence have not been reported. This study intends to explore the role of olaparib in the regulation of senescence in ovarian cancer cells. Methods The effects of olaparib on the senescence of ovarian cancer cells were detected by using the senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated heterochromatin aggregation (SAHF). Quantitative real-time polymerase chain reaction was used to analyze the senescence-associated secretory phenotype (SASP). Cell cycle and apoptosis were detected by flow cytometry. The effect of olaparib on tumor growth was analyzed in a nude mouse xenograft transplantation model. Results Long-term (6 days) treatment with olaparib (5 μM) significantly inhibited the growth of ovarian cancer cells, leading to arrest the cell cycle at G0/G1 phase, significant increase the number of positive SA-β-Gal stained cells and positive SAHF cells. The expression of P16 and retinoblastoma protein (p-RB) were significantly enhanced in SKOV3 cells under olaparib treated, meanwhile, the expression of P53 and p-RB were upregulated in A2780 cells. In OVCAR-3 cells, the expression of P53 was downregulated and p-RB was upregulated. Mice with SKOV3 xenograft transplantation was given olaparib (10 mg/kg/day) via abdominal cavity administration, the tumor volume was reduced (p
- Subjects :
- Senescence
Down-Regulation
Mice, Nude
Poly(ADP-ribose) Polymerase Inhibitors
Retinoblastoma Protein
Piperazines
Olaparib
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Nude mouse
Cell Line, Tumor
medicine
Animals
Humans
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p16
Ovarian Neoplasms
030219 obstetrics & reproductive medicine
biology
business.industry
Ovary
Retinoblastoma protein
Obstetrics and Gynecology
Neoplasms, Experimental
General Medicine
Cell cycle
medicine.disease
biology.organism_classification
Tumor Burden
Up-Regulation
Oncology
chemistry
Apoptosis
030220 oncology & carcinogenesis
PARP inhibitor
Cancer research
biology.protein
Phthalazines
Original Article
Female
Tumor Suppressor Protein p53
Ovarian cancer
business
Subjects
Details
- ISSN :
- 20050399 and 20050380
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Journal of Gynecologic Oncology
- Accession number :
- edsair.doi.dedup.....224c5efda4532820d3c4aa3dae094e7b