scholarly journals ZNF582 Methylation Predicts Better Radiotherapy Response of Cervical Cancer and ZNF582 Overexpression Reduces Radiosensitivity by Arresting the Cell Cycle in S Phase

Author(s):  
Nayiyuan Wu ◽  
Xiaoyun Zhang ◽  
Miaochen Zhu ◽  
Chao Fang ◽  
Xiaoting Liu ◽  
...  

Abstract Purpose: Our previous studies identified ZNF582 methylation (ZNF582m) level as a useful biomarker for cervical cancer screening, detection, and prognosis. The purpose of this study is to investigate the relationship between ZNF582m level and cervical cancer radiotherapy sensitivity and its underlying mechanism.Patients and Methods: This was a prospective multicenter clinical study, included two independent cohorts locally advanced cervical cancer patients. Exfoliated cervical cancer cells were collected pre-treatment and during treatment (after 24, 30, 36, 48, and 64 Gy) to test ZNF582m level, radiotherapy response evaluated according to RECIST Version. Results: In the first cohort, 22 cases achieved satisfied response, 28 exhibited modest response. Radiotherapy reduced ZNF582m level among all patients. Baseline ZNF582m was significantly higher in the satisfied response cases than in modest response cases, also, patients with high baseline ZNF582m (ZNF582m-high, n = 21) were more sensitive to radiotherapy than ZNF582m-low patients (n = 29), as evidenced by greater satisfied response rate (76.2% vs. 20.7%). An independent cohort confirmed above results. The magnitude of ZNF582m reduction was associated with a radiotherapeutic response, a subset of ZNF582m-low patients (5 of 28) exhibiting a transient increase in ZNF582m demonstrated greater radiosensitivity than other ZNF582m-low patients. ZNF582 overexpression induced cell cycle arrest in S phase.Conclusion: High ZNF582m level predicts better cervical cancer radiosensitivity, ZNF582 overexpression reduces radiosensitivity by cell cycle arrest.

2019 ◽  
Vol Volume 12 ◽  
pp. 10535-10545 ◽  
Author(s):  
Yani Chen ◽  
Juan Du ◽  
Yu Wang ◽  
Haiyan Shi ◽  
Qiuyu Jiang ◽  
...  

2016 ◽  
Vol 11 (4) ◽  
pp. 838 ◽  
Author(s):  
Ning Xia

<p class="Abstract">The present study was aimed at to demonstrate the antitumor effects of syringin in HeLa human cervical cancer cells. Its effects on apoptosis, cell cycle phase distribution as well as on cell migration were also examined. The effect on cell proliferation was evaluated by MTT assay, while as effects on colony formation were assessed using clonogenic assay. Syringin inhibited cancer cell growth in HeLa cells in a time-dependent as well as in a concentration-dependent manner. Syringin also led to inhibition of colony formation efficacy with complete suppression at 100 µM drug dose. Syringin could induce G2/M cell cycle arrest along with slight sub-G1 cell cycle arrest. HeLa cells began to emit red fluorescence as the dose of syringin increased from 0 µM in vehicle control to 100 µM. Syringin also inhibited cell migration in a dose-dependent manner with 100 µM dose of syringin leading to 100% inhibition of cell migration.</p><p> </p>


2018 ◽  
Vol 243 (14) ◽  
pp. 1133-1140
Author(s):  
Ling Chen ◽  
Ting Zhang ◽  
Qiuli Liu ◽  
Mei Tang ◽  
Yu’e Yang ◽  
...  

Buformin is a commonly used hypoglycemic agent, and numerous studies have shown that buformin has potent antitumor effects in several malignancies. In this study, we aimed to assess the cytotoxic effect of buformin combined with ionizing radiation (IR) on two human cervical cancer cell lines (Hela and Siha). Cytotoxicity was detected by colony formation assays; impacts on the cell cycle and apoptosis were detected by flow cytometric analyses. Changes in histone H2AX (γ-H2AX) phosphorylation and impacts on the AMPK/S6 pathway were also explored. Our data show that the combination of buformin and IR had a much stronger antiproliferative effect and resulted in more apoptosis than did buformin or IR alone. Combination treatment with a low dose of buformin (10 µM) and IR (4 Gy) caused G2/M-phase cell cycle arrest. Consistent with these findings, Western blotting showed that the combination of buformin and IR activated AMPK and suppressed S6. In addition, delayed disappearance of γ-H2AX was detected by immunofluorescence in cervical cancer cells treated with buformin plus IR. Taken together, the data indicate that the combination of a low concentration of buformin and IR increases the radiosensitivity of cervical cancer cells via cell cycle arrest and inhibition of DNA repair. Based on these results, we strongly support the use of buformin as an effective agent for improving IR treatment efficiency in the context of cervical cancer. Impact statement Our idea originated in the thought of discovering new effects of old drugs. Although this study is a basic research, it is very close to clinical treatment. Flow cytometry and immunofluorescence were used to verify that buformin increases radiosensitivity. We aimed to address one of the thorniest problems in treatment process. Based on discovering new effects of old drugs, it is feasible to use buformin as an anticancer drug in clinical application. This will provide new ideas for clinical treatment.


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