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Olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer
Zehua Wang,Jianwen Gao,Jiabing Zhou,Haiou Liu,Congjian Xu 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.2
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<0.01). Conclusion: Continuous low dosage administration of olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer.
Shuancang Yu,Xiaoyi Wang,Xiuyun Zhao,Deshuang Zhang,Yangjun Yu,Jiabing Xu,Fenglan Zhang 한국유전학회 2010 Genes & Genomics Vol.32 No.5
Pak‐choi (Brassica rapa L. ssp. chinensis Makino) is one of the most important vegetable, especially in southern China. Morphological traits of Pak‐choi vary widely, and the genetic basis of these variations is largely undescribed. In this study,we evaluated eighty Pak‐choi accessions for genetic diversity based on 29 morphological descriptors and 20 microsatellite (SSR) loci. Our data reveal a high level of diversity in this set of Pak‐choi accessions. Euclidean distance was used for cluster analysis. The UPGMA dendrogram grouped the Pakchoi accessions into five major clusters based on morphological characteristics. As expected, similar morphological characteristics grouped together in cluster branches. Further,population structure was explored to identify subpopulations based on allele frequency. Five groups were identified, and showed considerable correlation with the morphological clusters. Associations between SSR markers and agronomic traits were further investigated using a non‐parametric Kruskal–Wallis K‐test and six additional parametric models. Significant associations were found between 18 SSR loci and 28 morphological traits. This study provides evidence that marker‐trait associations can be validated in segregating populations and exploited through marker‐assisted selection.