Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression.
Targeting ornithine decarboxylase (ODC) inhibits esophageal squamous cell carcinoma progression.
复制标题
靶向鸟氨酸脱羧酶（ODC）抑制食管鳞状细胞癌进展。
DOI：
10.1038/s41698-017-0014-1
复制
发表时间：
2017
影响因子：
7.9
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
He W;Roh E;Yao K;Liu K;Meng X;Liu F;Wang P;Bode AM;Dong Z
探讨鸟氨酸脱羧酶在食管鳞状细胞癌进展中的作用，检验抗鸟氨酸脱羧酶治疗食管鳞状细胞癌的疗效。本研究采用免疫组化和Western blot方法检测鸟氨酸脱羧酶在食管鳞状细胞癌细胞系和组织中的表达规律。然后，我们利用shRNA和不可逆的鸟氨酸脱羧酶抑制剂二氟甲基鸟氨酸，研究了鸟氨酸脱羧酶在ESCC细胞中的功能。为了收集更多的临床前支持数据，采用人食管鳞状细胞癌患者来源的异种移植小鼠模型（C.B-17严重联合免疫缺陷小鼠）来测定二氟甲基鸟氨酸的体内抗肿瘤作用。我们的数据显示，与食管炎或正常邻近组织相比，食管鳞状细胞癌组织中鸟氨酸脱羧酶蛋白的表达增加。ODC shRNA多胺耗损不仅能抑制G2/M期食管鳞癌细胞，还能诱导细胞凋亡，进一步抑制食管鳞癌细胞的肿瘤发生。二氟甲基鸟氨酸治疗可减少食管鳞状细胞癌细胞和植入肿瘤的增殖，并诱导其凋亡，使肿瘤的大小和重量显著减小。本研究结果表明鸟氨酸脱羧酶是治疗食管鳞状细胞癌的一个有希望的靶点，二氟甲基鸟氨酸对食管鳞状细胞癌的治疗效果值得进一步的临床试验研究。阻断一种参与细胞合成必需化合物多胺的酶可能有助于治疗食管癌。来自美国明尼苏达大学荷梅尔研究所的董子刚及其同事发现，这种被称为鸟氨酸脱羧酶（ODC）的酶在食管鳞状细胞癌患者的肿瘤组织中表达水平升高。研究人员使用RNA干扰技术或一种叫做二氟甲基鸟氨酸（DFMO）的药物来阻断食管癌细胞中的ODC活性。在这两种情况下，治疗抑制了进一步的生长并诱导细胞死亡。DFMO治疗还减少了植入人类患者来源食管癌组织的小鼠肿瘤的大小和重量。DFMO已经被用作治疗非洲昏睡病和头发过度生长的药物，研究结果指出，它可能是癌症患者的一种治疗方法。
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. Blocking an enzyme involved in the cellular synthesis of essential compounds called polyamines could help treat esophageal cancer. Zigang Dong from the University of Minnesota’s Hormel Institute, USA, and colleagues showed that this enzyme, called ornithine decarboxylase (ODC), is expressed at elevated levels in tumor tissues taken from patients with esophageal squamous cell carcinoma. The researchers blocked ODC activity in esophageal cancer cells using either RNA interference techniques or a drug called difluoromethylornithine (DFMO). In both cases, the treatment suppressed further growth and induced cell death. DFMO treatment also reduced the size and weight of tumors in mice implanted with human patient-derived esophageal cancer tissue. The findings point DFMO, which is already used as a medication to treat African sleeping sickness and excessive hair growth, as a potential therapy for cancer patients.
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影响因子：
3.7
作者：
FREDLUND, JO;JOHANSSON, MC;OREDSSON, SM
通讯作者：
OREDSSON, SM
影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
3.5
作者：
Hayes CS;DeFeo-Mattox K;Woster PM;Gilmour SK
通讯作者：
Gilmour SK
DOI：
10.1073/pnas.90.16.7804
发表时间：
1993-08-15
影响因子：
11.1
作者：
BELLOFERNANDEZ, C;PACKHAM, G;CLEVELAND, JL
通讯作者：
CLEVELAND, JL
DOI：
10.1073/pnas.95.9.4997
发表时间：
1998-04-28
影响因子：
11.1
作者：
Jürgensmeier, JM;Xie, ZH;Reed, JC
通讯作者：
Reed, JC