Research Paper Volume 11, Issue 20 pp 9043—9059

T5224, RSPO2 and AZD5363 are novel drugs against functional pituitary adenoma

Sheng Zhong 1, 2, *, , Bo Wu 2, 4, *, , Jiahui Li 3, , Xinhui Wang 2, 5, , Shanshan Jiang 3, , Fangfei Hu 3, , Gaojing Dou 2, , Yuan Zhang 2, , Chunjia Sheng 2, , Gang Zhao 1, 2, , Yunqian Li 1, 2, #, , Yong Chen 1, 2, ,

  • 1 Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
  • 2 Clinical College, Jilin University, Changchun, China
  • 3 Pharmacy College, Jilin University, Chuangchun, China
  • 4 Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
  • 5 Department of Oncology, The First Hospital of Jilin University, Changchun, China
* Equal contribution
# Co-corresponding author

received: April 25, 2019 ; accepted: October 12, 2019 ; published: October 26, 2019 ;

https://doi.org/10.18632/aging.102372
How to Cite

Copyright © 2019 Zhong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We tested whether the drugs T5224, RSPO2, and AZD5363 exert therapeutic effects against functioning pituitary adenoma (FPA). We analysed the gene expression profiles of four FPA mRNA microarray datasets (GSE2175, GSE26966, GSE36314, and GSE37153) from the Gene Expression Omnibus database and identified genes differentially expressed in FPA vs control tissues. We then carried out Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction network analyses. We also measured the difference in expression of hub genes between human normal pituitary cells and FPA cells using qRT-PCR. Our in vitro colony-formation and MTT assays showed that cell viability, number, and the size of clonogenicities were all lower in the presence of T5224, RSPO2, or AZD536 than in controls. Moreover, flow cytometry experiments showed that the incidence of apoptosis was higher in the presence of T5224, RSPO2, or AZD5363 than among controls, and was increased by increasing the doses of the drugs. This suggests these drugs could be used as therapeutic agents to treat FPA. Finally, we found that cFos, WNT5A, NCAM1, JUP, AKT3, and ADCY1 are abnormally expressed in FPA cells compared to controls, which highlights these genes as potential prognostic and/or therapeutic targets.

Abbreviations

ATCC: American Type Culture Collection; ACTH: Adrenocorticotropic; AP-1: Activator protein-1; ADCY1: Adenylate cyclase 1; BP: Biological processes; BMP: Bone morphogenetic proteins; CC: Cell component; DEG: Differential expressed genes; DAVID: Database for Annotation, Visualization and Integrated Discovery; DMEM: Dulbecco’s modified Eagle’s medium; Eca-1: Esophageal carcinoma-1; FBS: Fetal bovine serum; FPA: Functioning pituitary adenomas; GO: Gene ontology; GH: Growth hormone; GEO: Gene Expression Omnibus; miRNAs: HMGA-targeting microRNAs; JUP: Junction plakoglobin,; KEGG: Kyoto encyclopedia of Genes and Genomes; LN1: Lymph node-positive; MF: Molecular function; nAChRs: Nicotinic acetylcholine receptors; NCAM1: Neural Cell Adhesion Molecule; PRL: Prolactinoma; PA: Pituitary adenomas; PKB: Protein kinase B; PCA PCA: Principal component analysis; PPI: Protein-protein interaction; RAC: Rectal adenocarcinoma; STRING: Search Tool for Retrieval of Interacting Genes; TSH: Thyroid-stimulating hormone; WHO: World Hearth Organization; WNT5A: Wnt member 5a; WT: Wilms’ tumor; β-ARs: β-Adrenergic receptors.