scholarly journals Lamin-A interacting protein Hsp90 is required for DNA damage repair and chemoresistance of ovarian cancer cells

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yixuan Wang ◽  
Quan Chen ◽  
Di Wu ◽  
Qifeng Chen ◽  
Guanghui Gong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Gynecologic Cancer ◽  
Dna Damage Repair ◽  
Xenograft Model ◽  
Ovarian Cancer Cells ◽  
Lamin A ◽  
Damage Repair ◽  
Mouse Xenograft Model

AbstractOvarian cancer is the most malignant gynecologic cancer. Previous studies found that lamin-A was associated with DNA damage repair proteins but the underlying mechanism remains unclear. We speculate that this may be related to its interacting proteins, such as Hsp90. The aim of this study is to investigate the effects of Hsp90 on DNA damage repair and chemoresistance of ovarian cancer cells. In our research, co-immunoprecipitation (co-IP) and mass spectrometry (MS) were used to identify proteins interacting with lamin-A and the interaction domain. Next, the relationship between lamin-A and Hsp90 was explored by Western blotting (WB) and immunofluorescence staining. Then, effect of Hsp90 inhibition on DNA damage repair was assessed through detecting Rad50 and Ku80 by WB. Furthermore, to test the roles of 17-AAG on cell chemosensitivity, CCK-8 and colony formation assay were carried out. Meanwhile, IC50 of cells were calculated, followed by immunofluorescence to detect DNA damage. At last, the mouse xenograft model was used in determining the capacity of 17-AAG and DDP to suppress tumor growth and metastatic potential. The results showed that lamin-A could interact with Hsp90 via the domain of lamin-A1-430. Besides, the distribution of Hsp90 could be affected by lamin-A. After lamin-A knockdown, Hsp90 decreased in the cytoplasm and increased in the nucleus, suggesting that the interaction between lamin-A and Hsp90 may be related to the nucleocytoplasmic transport of Hsp90. Moreover, inhibition of Hsp90 led to an obvious decrease in the expression of DSBs (DNA double-strand break) repair proteins, as well as cell proliferation ability upon DDP treatment and IC50 of DDP, causing more serious DNA damage. In addition, the combination of 17-AAG and DDP restrained the growth of ovarian cancer efficiently in vivo and prolonged the survival time of tumor-bearing mice.

scholarly journals Senescent peritoneal mesothelium induces a pro-angiogenic phenotype in ovarian cancer cells in vitro and in a mouse xenograft model in vivo

2015 ◽  
Vol 33 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Justyna Mikuła-Pietrasik ◽  
Patrycja Sosińska ◽  
Eryk Naumowicz ◽  
Konstantin Maksin ◽  
Hanna Piotrowska ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Ovarian Cancer Cells ◽  
Mouse Xenograft ◽  
Mouse Xenograft Model ◽  
Peritoneal Mesothelium

scholarly journals The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Wenwen Gao ◽  
Mengqiu Huang ◽  
Xi Chen ◽  
Jianping Chen ◽  
Zhiwei Zou ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nitrogen Oxide ◽  
Cancer Cells ◽  
Critical Role ◽  
Xenograft Model ◽  
Metabolic Reprogramming ◽  
Ovarian Cancer Cells ◽  
Metabolic Switch ◽  
Mouse Xenograft Model

AbstractOne of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.

scholarly journals Short-term starvation synergistically enhances cytotoxicity of Niraparib via Akt/mTOR signaling pathway in ovarian cancer therapy

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Wang Zhi ◽  
Suting Li ◽  
Yuting Wan ◽  
Fuwen Wu ◽  
Li Hong
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Side Effects ◽  
Molecular Mechanisms ◽  
Combined Treatment ◽  
Dna Damage Repair ◽  
Ovarian Cancer Cells ◽  
Short Term ◽  
Damage Repair ◽  
Combined Use

Abstract Background Short-term starvation (STS) has gradually been confirmed as a treatment method that synergistically enhances the effect of chemotherapy on malignant tumours. In clinical applications, there are still some limitations of poly (ADP-ribose) polymerase inhibitors (PARPi), including understanding their effectiveness and side effects. Here, we sought to investigate the effect and mechanism of the combined use of STS and niraparib in the treatment of ovarian cancer. Methods In in vitro experiments, SKOV3 and A2780 ovarian cancer cells were treated with STS and niraparib alone or in combination. Cell viability was assessed with CCK-8, and cell cycle, apoptosis, DNA damage repair and autophagy were examined to explore the molecular mechanisms. Akt and mTOR inhibitors were used to examine any changes in DNA damage repair levels. Xenograft animal models were treated with STS and niraparib, and HE staining and immunohistochemistry were performed to examine the effects. Results The combined use of STS and niraparib inhibited cell proliferation and increased apoptosis more than niraparib application alone. In addition, compared with the niraparib group, the STS + niraparib group had increased G2/M arrest, DNA damage and autophagy, which indicated that STS pretreatment enhanced the cytotoxicity of niraparib. In animal experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib. In in vivo experiments, STS did not affect the growth of transplanted tumours, but the combined treatment synergistically enhanced the cytotoxicity of niraparib and reduced the small intestinal side effects caused by niraparib chemotherapy. Conclusion STS pretreatment can synergistically enhance the cytotoxicity of niraparib. STS + niraparib is a potentially effective strategy in the maintenance therapy of ovarian cancer.

scholarly journals PML silencing inhibits cell proliferation and induces DNA damage in cultured ovarian cancer cells

2017 ◽  
Vol 7 (1) ◽  
pp. 29-35 ◽  
Author(s):  
Sheng-Bing Liu ◽  
Zhong-Fei Shen ◽  
Yan-Jun Guo ◽  
Li-Xian Cao ◽  
Ying Xu
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cancer Cells ◽  
Ovarian Cancer Cells

scholarly journals DNA Damage-Binding Complex Recruits HDAC1 to Repress Bcl-2 Transcription in Human Ovarian Cancer Cells

2013 ◽  
Vol 12 (3) ◽  
pp. 370-380 ◽  
Author(s):  
Ran Zhao ◽  
Chunhua Han ◽  
Eric Eisenhauer ◽  
John Kroger ◽  
Weiqiang Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer

scholarly journals MTA1 promotes cell proliferation via DNA damage repair in epithelial ovarian cancer

2014 ◽  
Vol 13 (4) ◽  
pp. 10269-10278 ◽  
Author(s):  
Q.Y. Yang ◽  
J.H. Li ◽  
Q.Y. Wang ◽  
Y. Wu ◽  
J.L. Qin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Epithelial Ovarian Cancer ◽  
Dna Damage Repair ◽  
Damage Repair

scholarly journals Fucosterol Suppresses the Progression of Human Ovarian Cancer by Inducing Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

Marine Drugs ◽  
2020 ◽  
Vol 18 (5) ◽  
pp. 261 ◽  
Author(s):  
Hyocheol Bae ◽  
Jin-Young Lee ◽  
Gwonhwa Song ◽  
Whasun Lim
Keyword(s):  
Ovarian Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Anticancer Properties

Ovarian cancer is difficult to diagnose early and has high rates of relapse and mortality. Therefore, the treatment of ovarian cancer needs to be improved. Recently, several studies have been conducted in an attempt to develop anticancer drugs from naturally derived ingredients. Compared to traditional chemotherapy, natural compounds can overcome drug resistance with lower side effects. Fucosterol, a phytosterol present in brown algae, reportedly possesses many bioactive effects, including anticancer properties. However, the anticancer effects of fucosterol in ovarian cancer remain unexplored. Therefore, we investigated the effects of fucosterol on progression in human ovarian cancer cells. Fucosterol inhibited cell proliferation and cell-cycle progression in ovarian cancer cells. Additionally, fucosterol regulated the proliferation-related signaling pathways, the production of reactive oxygen species, mitochondrial function, endoplasmic reticulum stress, angiogenesis, and calcium homeostasis. Moreover, it decreased tumor formation in a zebrafish xenograft model. These results indicate that fucosterol could be used as a potential therapeutic agent in ovarian cancer.

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