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马来酸替加色罗通过抑制过氧化物酶体途径抑制食管鳞状细胞癌增殖。

Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway.

作者信息

Wu Xiangyu, Wang Zitong, Jiang Yanan, Zhou Hao, Li Ang, Wei Yaxing, Bao Zhuo, Wang Donghao, Zhao Jimin, Chen Xinhuan, Guo Yaping, Dong Zigang, Liu Kangdong

机构信息

Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.

出版信息

Front Oncol. 2021 Aug 4;11:683241. doi: 10.3389/fonc.2021.683241. eCollection 2021.

DOI:10.3389/fonc.2021.683241
PMID:34422635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8372369/
Abstract

Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of esophageal cancer (EC). ESCC accounts for 90% of EC. Recurrence after primary treatment is the main reason for poor survival. Therefore, recurrence prevention is a promising strategy for extending the 5-year survival rate. Here, we found tegaserod maleate could inhibit ESCC proliferation both and . Proteomics analysis revealed that tegaserod maleate suppressed the peroxisome signaling pathway, in which the key molecules peroxisome membrane protein 11B (PEX11B) and peroxisome membrane protein 13 (PEX13) were downregulated. The immunofluorescence, catalase activity assay, and reactive oxygen species (ROS) confirmed that downregulation of these proteins was related to impaired peroxisome function. Furthermore, we found that PEX11B and PEX13 were highly expressed in ESCC, and knockout of PEX11B and PEX13 further demonstrated the antitumor effect of tegaserod maleate. Importantly, tegaserod maleate repressed ESCC tumor growth in a patient-derived xenograft (PDX) model . Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.

摘要

食管鳞状细胞癌（ESCC）和食管腺癌（EAC）是食管癌（EC）的两种主要类型。ESCC占EC的90%。初次治疗后的复发是生存率低的主要原因。因此，预防复发是提高5年生存率的一种有前景的策略。在此，我们发现马来酸替加色罗可在体内和体外抑制ESCC增殖。蛋白质组学分析显示，马来酸替加色罗抑制过氧化物酶体信号通路，其中关键分子过氧化物酶体膜蛋白11B（PEX11B）和过氧化物酶体膜蛋白13（PEX13）表达下调。免疫荧光、过氧化氢酶活性测定和活性氧（ROS）证实这些蛋白的下调与过氧化物酶体功能受损有关。此外，我们发现PEX11B和PEX13在ESCC中高表达，敲除PEX11B和PEX13进一步证明了马来酸替加色罗的抗肿瘤作用。重要的是，马来酸替加色罗在患者来源的异种移植（PDX）模型中抑制ESCC肿瘤生长。我们的研究结果确凿地表明，马来酸替加色罗通过抑制过氧化物酶体途径抑制ESCC的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/20c3b66e0d73/fonc-11-683241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/027c05b7d568/fonc-11-683241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/3ee2f1c2da2e/fonc-11-683241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/a12b2acd31b1/fonc-11-683241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/f04a8a6d5c3e/fonc-11-683241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/a890a1ad8f6c/fonc-11-683241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/eed3170fa1f8/fonc-11-683241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/20c3b66e0d73/fonc-11-683241-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/027c05b7d568/fonc-11-683241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/3ee2f1c2da2e/fonc-11-683241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/a12b2acd31b1/fonc-11-683241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/f04a8a6d5c3e/fonc-11-683241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/a890a1ad8f6c/fonc-11-683241-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/eed3170fa1f8/fonc-11-683241-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c03/8372369/20c3b66e0d73/fonc-11-683241-g007.jpg

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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

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Gastroenterology. 2019-4-9

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