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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.

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        Novel Organic/Inorganic Hybrid Star Polymer Surface-Crosslinked with Polyhedral Oligomeric Silsesquioxane

        Jingyan Zhang,Dong Si,Shifeng Wang,Hao Liu,Xiaoming Chen,Haiou Zhou,Mingdi Yang,Guoying Zhang 한국고분자학회 2020 Macromolecular Research Vol.28 No.2

        Novel organic/inorganic hybrid star polymer was prepared dually crosslinked within inner-core via divinylbenzene (DVB) and outer-surface via octafunctional polyhedral oligomeric silsesquioxane (POSS). Core cross-linked star polymers bearing dialkynyl-terminated polystyrene arms, (dialkynyl-PS)n-CCL, were synthesized at first by the atom transfer radical polymerization (ATRP) of DVB using α,α-dialkynyl-terminated PS macroinitiator, followed by the subsequent fractionation. Under high dilution conditions, (dialkynyl-PS)n-CCL was subjected to surface cross-linking with octa(3- azidopropyl) polyhedral oligomeric silsesquioxane, POSS-(N3)8, via click reaction, affording POSS-functionalized hybrid polymer doubly cross-linked within core and surface regions, SCL-(PS)n-CCL. FT-IR, 1H NMR, GPC, and elemental analysis results revealed that on average, the obtained hybrid polymer possesses a cross-linked PDVB inner core, ~14 linear PS arms (the MW per arm of 5.1 kDa), and ~4-5 POSS moieties at outer surface. Differential scanning calorimetry (DSC) thermograms and thermogravimetric analysis (TGA) revealed that after surface cross-linking the thermal stability of SCL-(PS)n-CCL is considerably improved. This work provides a proof-of-concept example for the preparation of dually cross-linked hybrid star polymer, which represents a novel category of organic/inorganic composite materials with unique chain architectures.

      • KCI등재

        An In situ Forming Hydrogel Based on Photo-Induced Hydrogen Bonding

        Jingyan Zhang,Shifeng Wang,Zeren Zhao,Dong Si,Haiou Zhou,Mingdi Yang,Xianbiao Wang 한국고분자학회 2020 Macromolecular Research Vol.28 No.12

        Stimulus-induced in situ forming hydrogels possess the characteristics of easy management and minimal invasiveness via simple injection at target sites with a liquid and easy forming bulk gels. In the present study, a photoreactive monomer, N'-(2-nitrobenzyl)-N-acryloyl glycinamide (NBNAGA) was introduced to modify polyacrylamide (PAM) hydrogel preparation with stimuli responsiveness. Firstly, poly(acrylamide-co-N'-(2-nitrobenzyl)-N-acryloyl glycinamide), P(AM-co-NBNAGA), copolymer solution was prepared via reversible addition fragmentation chain transfer (RAFT) polymerization using the monomers mixture of AM, NBNAGA, and N,N'- methylene bis-acrylamide (BIS). The obtained polymer solution with viscous, transparent, and flowable appearance contained weak single hydrogen bonding and slight chemical crosslinking in a microscopic perspective. Secondly, without further purification, after irradiation using UV light at 365 nm, poly(acrylamide-co-N-acryloyl glycinamide) (P(AM-co-NAGA)) hydrogel conveniently in situ formed due to the cleavage of o-nitrobenzyl groups and the corresponding emergency of dual hydrogen bonding among “uncaged” dual amide moieties. P(AM-co-NAGA) hydrogel depicted both favorable temperature sensitivity and self-healing properties, then the heating induced in vitro release profiles of doxorubicin (DOX) was analyzed.

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