Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression

被引：23

作者：

He, Wei ^{[1
,2
,3
,4
]}

Roh, Eunmiri ^{[1
]}

Yao, Ke ^{[1
]}

Liu, Kangdong ^{[3
,4
]}

Meng, Xing ^{[3
,4
]}

Liu, Fangfang ^{[3
,4
]}

Wang, Penglei ^{[3
,4
]}

Bode, Ann M. ^{[1
]}

Dong, Zigang ^{[1
,3
,4
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

[2] Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China

[3] Zhengzhou Univ, Basic Med Coll, Zhengzhou 450001, Henan, Peoples R China

[4] China US Henan Hormel Canc Inst, Zhengzhou 450008, Henan, Peoples R China

来源：

NPJ PRECISION ONCOLOGY | 2017年 / 1卷

基金：

美国国家卫生研究院;

关键词：

CANCER CHEMOPREVENTION; MESSENGER-RNA; COLON-CANCER; S-PHASE; EXPRESSION; CYCLE; APOPTOSIS; ARREST; MODELS; GENE;

D O I：

10.1038/s41698-017-0014-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To explore the function of ornithine decarboxylase in esophageal squamous cell carcinoma progression and test the effectiveness of anti-ornithine decarboxylase therapy for esophageal squamous cell carcinoma. In this study, we examined the expression pattern of ornithine decarboxylase in esophageal squamous cell carcinoma cell lines and tissues using immunohistochemistry and Western blot analysis. Then we investigated the function of ornithine decarboxylase in ESCC cells by using shRNA and an irreversible inhibitor of ornithine decarboxylase, difluoromethylornithine. To gather more supporting pre-clinical data, a human esophageal squamous cell carcinoma patient-derived xenograft mouse model (C. B-17 severe combined immunodeficient mice) was used to determine the antitumor effects of difluoromethylornithine in vivo. Our data showed that the expression of the ornithine decarboxylase protein is increased in esophageal squamous cell carcinoma tissues compared with esophagitis or normal adjacent tissues. Polyamine depletion by ODC shRNA not only arrests esophageal squamous cell carcinoma cells in the G2/M phase, but also induces apoptosis, which further suppresses esophageal squamous cell carcinoma cell tumorigenesis. Difluoromethylornithine treatment decreases proliferation and also induces apoptosis of esophageal squamous cell carcinoma cells and implanted tumors, resulting in significant reduction in the size and weight of tumors. The results of this study indicate that ornithine decarboxylase is a promising target for esophageal squamous cell carcinoma therapy and difluoromethylornithine warrants further study in clinical trials to test its effectiveness against esophageal squamous cell carcinoma.

引用

页数：11

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