Oncotarget

Research Papers:

PPMP, a novel tubulin-depolymerizing agent against esophageal cancer in patient-derived tumor xenografts

Yuqiao Sheng, Kangdong Liu, Qiong Wu, Naomi Oi, Hanyong Chen, Kanamata Reddy, Yanan Jiang, Ke Yao, Haitao Li, Wei Li, Yi Zhang, Mohammad Saleem, Wei-Ya Ma, Ann M. Bode, Ziming Dong and Zigang Dong _

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Oncotarget. 2016; 7:30977-30989. https://doi.org/10.18632/oncotarget.9050

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Abstract

Yuqiao Sheng1,2,3,*, Kangdong Liu1,2,4,*, Qiong Wu1,4,*, Naomi Oi2, Hanyong Chen2, Kanamata Reddy2, Yanan Jiang1, Ke Yao2, Haitao Li2, Wei Li2, Yi Zhang1,2,3,4, Mohammad Saleem2, Wei-Ya Ma2, Ann M. Bode2, Ziming Dong1, Zigang Dong1,2,4

1Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China

2The Hormel Institute, University of Minnesota, Austin, Minnesota, USA

3The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China

4China-US (Henan) Hormel Cancer Institute, ZhengZhou, Henan, China

*These authors contributed equally to this work

Correspondence to:

Zigang Dong, e-mail: [email protected]

Ziming Dong, e-mail: [email protected]

Keywords: tubulin-depolymerizing agent, esophageal cancer, patient-derived tumor xenograft

Received: December 17, 2015     Accepted: April 10, 2016     Published: April 27, 2016

ABSTRACT

Esophageal cancer is one of the least studied and deadliest cancers worldwide with a poor prognosis due to limited options for treatment. Chemotherapy agents such as the microtubule-targeting compounds are the mainstay of palliation for advanced esophageal cancer treatment. However, the toxicity and side effects of tubulin-binding agents (TBAs) have promoted the development of novel, more potent but less toxic TBAs. Herein, we identified 2-[4-(3,4-dimethoxyphenyl)-3-methyl-1H-pyrazol-5-yl]-5-[(2-methylprop-2-en-1-yl)oxy] phenol (PPMP) as a novel TBA for esophageal cancer treatment. PPMP markedly inhibited tubulin polymerization, and decreased viability and anchorage-independent growth of esophageal cancer cell lines, effects that were accompanied by G2/M arrest and apoptosis. Importantly, we produced patient-derived esophageal cancer xenografts to evaluate the therapeutic effect of PPMP in a setting that best mimics the clinical context in patients with esophageal cancer. Overall, we identified PPMP as a novel microtubule-destabilizing compound and as a new therapeutic agent against esophageal carcinoma.


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