Open AccessGLP1R inhibits the progression of endometrial carcinoma through activation of cAMP / PKA pathway
Author(s) -
Li Wu,
Gu Yanpin,
Liu Songjun,
Ruan Fan,
Lv Wen
Publication year - 2022
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.24604
Subject(s) - downregulation and upregulation , signal transduction , cyclic adenosine monophosphate , chemistry , cell growth , apoptosis , transfection , protein kinase a , biology , microbiology and biotechnology , cell culture , kinase , receptor , biochemistry , gene , genetics
Background This study strived to explore the role and mechanism of glucagon‐like peptide‐1 receptor (GLP1R) in endometrial carcinoma (EC). Methods In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95‐2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5‐ethynyl‐2′‐deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p‐PKA, and PKA) were determined by enzyme‐linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC. Result According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway. Conclusion Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.