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  3. Investigation of the potential role of TGR5 in pancreatic cancer by a comprehensive molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics

Investigation of the potential role of TGR5 in pancreatic cancer by a comprehensive molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics

  • Discov Oncol. 2022 Jun 11;13(1):46. doi: 10.1007/s12672-022-00504-2.
Yangyang Lei  # 1 2,  Guoping Li  # 1 2 3,  Jianke Li 1 2,  Shanshan Gao 1 2,  Ming Lei 4,  Gaoquan Gong 1 2 3,  Changyu Li 1 2 3,  Yi Chen 1 2 3,  Chenggang Wang 5 6 7,  Xiaolin Wang 8 9 10
Affiliations

Affiliations

  • 1 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 2 Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
  • 3 National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China.
  • 4 Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 5 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. wang.chenggang@zs-hospital.sh.cn.
  • 6 Shanghai Institute of Medical Imaging, Shanghai, 200032, China. wang.chenggang@zs-hospital.sh.cn.
  • 7 National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China. wang.chenggang@zs-hospital.sh.cn.
  • 8 Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China. fduwangxiaolin@163.com.
  • 9 Shanghai Institute of Medical Imaging, Shanghai, 200032, China. fduwangxiaolin@163.com.
  • 10 National Clinical Research Center for Interventional Medicine, Shanghai, 200032, China. fduwangxiaolin@163.com.
  • # Contributed equally.
PMID: 35689739 DOI: 10.1007/s12672-022-00504-2
Abstract

Background: Takeda G protein receptor 5 (TGR5) is widely recognized as a potential drug target for the treatment of metabolic diseases. TGR5 is not only a metabolic regulator, but also has a potential role that participating in developing and progressing of gastrointestinal Cancer. We aimed to investigate the potential role of TGR5 in pancreatic Cancer by utilizing molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics.

Methods: Herein, we assessed pancreatic Cancer proliferation, migration and invasion in response to TGR5 antagonist SBI-115 in vitro experiments. Cell death was examined by using TUNEL assay on agarose-embedded sections. Then we investigated the effects of TGR5 on PANC-1 and BXPC3 cells via transmission electron microscopy (TEM). Moreover, LC-MS-based metabolomics was performed to explore the potential underlying mechanisms of TGR5 in pancreatic Cancer. The correlations between TGR5 and the metabolism-related genes were further analysed by GEPIA 2 database.

Results: We found the proliferation capacities were decreased significantly in PANC-1 and BXPC3 cells after the treatment of SBI-115 for 48 h. The results of TUNEL assay showed that antagonism of TGR5 by SBI-115 had a remarkable effect on inducing cell death. Analysis of TEM demonstrated that SBI-115 treatment could impair the morphology of mitochondria in most PANC-1 and BXPC3 cells. The LC-MS-based analyses revealed that antagonism of TGR5 could alter the metabolic profiles of PANC-1 cells in vitro. Moreover, TGR5 was associated with some metabolism-related genes in pancreatic Cancer.

Conclusion: Our data suggests that antagonism of TGR5 may suppress cell proliferation and induce Apoptosis in pancreatic Cancer cells. TGR5 may affect the metabolism of pancreatic Cancer, and TGR5 would be an attractive target for pancreatic Cancer treatment.

Keywords

Liquid chromatography mass spectrometry; Mitochondria; Pancreatic cancer; SBI-115; TGR5.

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