The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines’ in-vitro and in-vivo xenografts

2013 ◽  
pp. 1 ◽  
Author(s):  
Mélanie Deberne ◽  
Antonin Levy ◽  
Michele Mondini ◽  
Philippe Dessen ◽  
Sonia Vivet ◽  
...  
Author(s):  
Zongjuan Li ◽  
Yang Zhang ◽  
Silei Sui ◽  
Yijun Hua ◽  
Anshi Zhao ◽  
...  

Abstract Background Radiotherapy is regarded as a milestone for the cure of cervical cancer. However, clinical outcome heavily be hindered by radioresistance. So, exploring the underlying mechanism of radioresistance, and find potential target, well deserve fully emphasis. Methods In this study, we developed two novel radiation resistance cervical cancer cell lines, which could mimic clinical radioresistance. In order to find new potential targets, RNA-Seq, database analysis, streptavidin-agarose and LC/MS were used. Pull-down, luciferase and rescue assays were conducted to explore the regulatory mechanisms. To further evaluate the correlation between therapeutic responses and HMGB3/hTERT expression, 172 cervical cancer patients were recruited. Results Knockdown of HMGB3 significantly inhibit the DNA damage repair and induced more γH2AX foci, leading to enhanced chemo- and radio-sensitivity in vitro and in vivo, whereas HMGB3 overexpression has the opposite effects. HMGB3 promotes cell growth and radioresistance by transcriptionally up-regulating hTERT via the specifical binding of HMGB3 at the hTERT promoter region from − 902 to − 321. HMGB3 knockdown-mediated radiosensitization could be reversed by the overexpressed hTERT in both cervical cancer cell lines and xenograft tumor mouse model. Furthermore, clinical data from 172 cervical cancer patients proved that there was a positive correlation between HMGB3 and hTERT expression, and high expression of HMGB3/hTERT predicted poor response to radiotherapy, worse TNM stages and shorter survival time. Conclusion Here, we have identified HMGB3/hTERT signaling axis as a new target for cervical cancer radioresistance. Our results provide new insights into the mechanism of cervical cancer radioresistance and indicate that targeting the HMGB3/hTERT signaling axis may benefit cervical cancer patients.


2016 ◽  
Vol 94 (5) ◽  
pp. 526-533 ◽  
Author(s):  
Yan Zhao ◽  
Xinyu Wang ◽  
Lei Li ◽  
Changzhong Li

The clinical management of cervical cancer remains a challenge and the development of new treatment strategies merits attention. However, the discovery and development of novel compounds can be a long and labourious process. Drug repositioning may circumvent this process and facilitate the rapid translation of hypothesis-driven science into the clinics. In this work, we show that a FDA-approved antibiotic, doxycycline, effectively targets human papillomavirus (HPV) positive and negative cervical cancer cells in vitro and in vivo. Doxycycline significantly inhibits proliferation of a panel of cervical cancer cell lines. It also induces apoptosis of cervical cancer cells in a time- and dose-dependent manner. In addition, the apoptosis induced by doxycycline is through caspase-dependent pathway. Mechanism studies demonstrate that doxycycline affects oxygen consumption rate, glycolysis, and reduces ATP levels in cervical cancer cells. In HeLa xenograft mouse model, doxycycline significantly inhibits growth of tumour. Our in vitro and in vivo data clearly demonstrate the inhibitory effects of doxycycline on the growth and survival of cervical cancer cells. Our work provides the evidence that doxycycline can be repurposed for the treatment of cervical cancer and targeting energy metabolism may represent a potential therapeutic strategy for cervical cancer.


1999 ◽  
Vol 10 (1) ◽  
pp. 75
Author(s):  
Hye Sung Moon ◽  
Hye Young Park ◽  
Seung Chul Kim ◽  
Sun Hee Yang ◽  
Soo Yeon Kim ◽  
...  

2011 ◽  
Vol 130 (8) ◽  
pp. 1925-1936 ◽  
Author(s):  
Hun Soon Jung ◽  
Ozgur Cem Erkin ◽  
Mi Jeong Kwon ◽  
Seok Hyung Kim ◽  
Jae In Jung ◽  
...  

2016 ◽  
Vol 14 (3) ◽  
pp. 2187-2193 ◽  
Author(s):  
Qin Qin ◽  
Zheng-Ai Xiong ◽  
Ying Liu ◽  
Chen-Guo Yao ◽  
Wei Zhou ◽  
...  

Cancer ◽  
1993 ◽  
Vol 71 (11) ◽  
pp. 3717-3725 ◽  
Author(s):  
Roberto Angioli ◽  
Bernd-Uwe Sevin ◽  
James P. Perras ◽  
Hervy E. Averette ◽  
Ossi R. Koechli ◽  
...  

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