Abstract | OBJECTIVE: 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 μ) 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<0.01). CONCLUSION: Continuous low dosage administration of olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer.
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Authors | Zehua Wang, Jianwen Gao, Jiabing Zhou, Haiou Liu, Congjian Xu |
Journal | Journal of gynecologic oncology
(J Gynecol Oncol)
Vol. 30
Issue 2
Pg. e26
(Mar 2019)
ISSN: 2005-0399 [Electronic] Korea (South) |
PMID | 30740957
(Publication Type: Journal Article)
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Copyright | Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology. |
Chemical References |
- CDKN2A protein, human
- Cyclin-Dependent Kinase Inhibitor p16
- Phthalazines
- Piperazines
- Poly(ADP-ribose) Polymerase Inhibitors
- Retinoblastoma Protein
- Tumor Suppressor Protein p53
- olaparib
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Topics |
- Animals
- Cell Line, Tumor
- Cellular Senescence
(drug effects)
- Cyclin-Dependent Kinase Inhibitor p16
(drug effects)
- Down-Regulation
- Female
- Humans
- Mice, Nude
- Neoplasms, Experimental
- Ovarian Neoplasms
(pathology)
- Phthalazines
(pharmacology)
- Piperazines
(pharmacology)
- Poly(ADP-ribose) Polymerase Inhibitors
(pharmacology)
- Retinoblastoma Protein
(drug effects)
- Tumor Burden
(drug effects)
- Tumor Suppressor Protein p53
(metabolism)
- Up-Regulation
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