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 Li³, Xinhui Wang^2,⁵, Shanshan Jiang³, Fangfei Hu³, Gaojing Dou², Yuan Zhang², Chunjia Sheng², Gang Zhao^1,², Yunqian Li^1,², Yong Chen^1,²

¹Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
²Clinical College, Jilin University, Changchun, China
³Pharmacy College, Jilin University, Chuangchun, China
⁴Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
⁵Department of Oncology, The First Hospital of Jilin University, Changchun, China

* Equal contribution

# Co-corresponding author

Received: April 25, 2019Accepted: October 12, 2019Published: October 26, 2019

https://doi.org/10.18632/aging.102372

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.