Oncotarget

Research Papers:

TAK1 inhibitor 5Z-7-oxozeaenol sensitizes cervical cancer to doxorubicin-induced apoptosis

Shan Guan, Jiaxiong Lu, Yanling Zhao, Sarah E. Woodfield, Huiyuan Zhang, Xin Xu, Yang Yu, Jing Zhao, Shayahati Bieerkehazhi, Haoqian Liang, Jianhua Yang, Fuchun Zhang and Surong Sun _

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Oncotarget. 2017; 8:33666-33675. https://doi.org/10.18632/oncotarget.16895

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Abstract

Shan Guan1,2, Jiaxiong Lu2, Yanling Zhao2, Sarah E. Woodfield3, Huiyuan Zhang2, Xin Xu2, Yang Yu2, Jing Zhao1, Shayahati Bieerkehazhi4, Haoqian Liang2,5, Jianhua Yang2, Fuchun Zhang1, Surong Sun1

1Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, Xinjiang 830046, China

2Texas Children’s Cancer Center, Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA

3Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA

4Department of Labour Hygiene and Sanitary Science, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang 830011, China

5School of Pharmacy, Zhengzhou University, Zhengzhou, Henan 450001, China

Correspondence to:

Surong Sun, email: sr_sun2005@163.com

Fuchun Zhang, email: zfcxju@xju.edu.cn

Keywords: cervical cancer, TAK1 inhibitor, 5Z-7-oxozeaenol, chemotherapy, doxorubicin

Received: February 22, 2017     Accepted: March 28, 2017     Published: April 06, 2017

ABSTRACT

Aberrant activation of nuclear factor-κB (NF-κB) allows cancer cells to escape chemotherapy-induced cell death and acts as one of the major mechanisms of acquired chemoresistance in cervical cancer. TAK1, a crucial mediator that upregulates NF-κB activation in response to cellular genotoxic stress, is required for tumor cell viability and survival. Herein, we examined whether TAK1 inhibition is a potential therapeutic strategy for treating cervical cancer. We found that TAK1 inhibitor 5Z-7-oxozeaenol significantly augmented the cytotoxic effects of Dox in a panel of cervical cancer cell lines. Treatment with 5Z-7-oxozeaenol hindered Dox-induced NF-κB activation and promoted Dox-induced apoptosis in cervical cancer cells. Moreover, 5Z-7-oxozeaenol showed similar effects in both positive and negative human papillomavirus-infected cervical cancer cells. Taken together, our results provide evidence that TAK1 inhibition significantly sensitizes cervical cancer cells to chemotherapy-induced cell death and supports the use of TAK1 inhibitor with current chemotherapies in the clinic for patients with refractory cervical cancer.


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