通过全面的分子实验和基于液相色谱-质谱联用（LC-MS）的代谢组学研究TGR5在胰腺癌中的潜在作用。
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.
作者信息
Lei Yangyang, Li Guoping, Li Jianke, Gao Shanshan, Lei Ming, Gong Gaoquan, Li Changyu, Chen Yi, Wang Chenggang, Wang Xiaolin
机构信息
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
出版信息
Discov Oncol. 2022 Jun 11;13(1):46. doi: 10.1007/s12672-022-00504-2.
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.
背景
武田G蛋白受体5（TGR5）被广泛认为是治疗代谢性疾病的潜在药物靶点。TGR5不仅是一种代谢调节因子，而且在胃肠道癌的发生和发展中具有潜在作用。我们旨在通过分子实验和基于液相色谱-质谱联用（LC-MS）的代谢组学研究TGR5在胰腺癌中的潜在作用。
方法
在此，我们在体外实验中评估了TGR5拮抗剂SBI-115对胰腺癌增殖、迁移和侵袭的影响。通过在琼脂糖包埋切片上使用TUNEL法检测细胞死亡情况。然后我们通过透射电子显微镜（TEM）研究TGR5对PANC-1和BXPC3细胞的影响。此外，进行基于LC-MS的代谢组学研究以探索TGR5在胰腺癌中的潜在作用机制。通过GEPIA 2数据库进一步分析TGR5与代谢相关基因之间的相关性。
结果
我们发现用SBI-115处理48小时后，PANC-1和BXPC3细胞的增殖能力显著降低。TUNEL分析结果表明，SBI-115拮抗TGR5对诱导细胞死亡有显著作用。TEM分析表明，SBI-115处理可损害大多数PANC-1和BXPC3细胞中线粒体的形态。基于LC-MS的分析显示，拮抗TGR5可改变体外培养的PANC-1细胞的代谢谱。此外，TGR5与胰腺癌中的一些代谢相关基因有关。
结论
我们的数据表明，拮抗TGR5可能抑制胰腺癌细胞的增殖并诱导其凋亡。TGR5可能影响胰腺癌的代谢，TGR5将是胰腺癌治疗的一个有吸引力的靶点。
Zotero 插件