Frontiers in Oncology (Aug 2021)
Tegaserod Maleate Inhibits Esophageal Squamous Cell Carcinoma Proliferation by Suppressing the Peroxisome Pathway
- Xiangyu Wu,
- Zitong Wang,
- Yanan Jiang,
- Yanan Jiang,
- Yanan Jiang,
- Yanan Jiang,
- Hao Zhou,
- Ang Li,
- Ang Li,
- Yaxing Wei,
- Zhuo Bao,
- Zhuo Bao,
- Donghao Wang,
- Donghao Wang,
- Jimin Zhao,
- Jimin Zhao,
- Jimin Zhao,
- Xinhuan Chen,
- Xinhuan Chen,
- Yaping Guo,
- Yaping Guo,
- Zigang Dong,
- Zigang Dong,
- Zigang Dong,
- Zigang Dong,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu,
- Kangdong Liu
Affiliations
- Xiangyu Wu
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Zitong Wang
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Yanan Jiang
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Yanan Jiang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Yanan Jiang
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Yanan Jiang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Hao Zhou
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Ang Li
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Ang Li
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Yaxing Wei
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Zhuo Bao
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Zhuo Bao
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Donghao Wang
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Donghao Wang
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Jimin Zhao
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Jimin Zhao
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Jimin Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Xinhuan Chen
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Xinhuan Chen
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Yaping Guo
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Yaping Guo
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Zigang Dong
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Zigang Dong
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Zigang Dong
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Zigang Dong
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
- Kangdong Liu
- Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- Kangdong Liu
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Kangdong Liu
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Kangdong Liu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
- Kangdong Liu
- Cancer Chemoprevention International Collaboration Laboratory, Zhengzhou, China
- DOI
- https://doi.org/10.3389/fonc.2021.683241
- Journal volume & issue
-
Vol. 11
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 in vivo and in vitro. 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 in vivo. Our findings conclusively demonstrated that tegaserod maleate inhibits the proliferation of ESCC by suppressing the peroxisome pathway.
Keywords
- esophageal squamous cell carcinoma
- tegaserod maleate
- proteome
- peroxisome
- peroxisome membrane protein 11B
- peroxisome membrane protein 13
