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Published on: March 21, 2017
T5224, RSPO2 and AZD5363 are novel drugs against functional pituitary adenoma
Sheng Zhong1,2, Bo Wu2,3, Jiahui Li4
1Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.
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.
Insights
Three drugs, T5224, RSPO2, and AZD5363, show therapeutic potential against functioning pituitary adenoma (FPA). These agents reduced tumor cell viability and increased apoptosis in vitro, indicating promise for FPA treatment.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Functioning pituitary adenoma (FPA) poses a significant clinical challenge.
- Identifying novel therapeutic targets for FPA is crucial.
Purpose of the Study:
- To evaluate the therapeutic efficacy of T5224, RSPO2, and AZD5363 against FPA.
- To identify potential molecular targets and biomarkers for FPA treatment.
Main Methods:
- Analysis of FPA gene expression datasets from the Gene Expression Omnibus database.
- In vitro assays including colony formation, MTT, and flow cytometry.
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) for hub gene expression analysis.
Main Results:
- T5224, RSPO2, and AZD5363 significantly reduced FPA cell viability, proliferation, and clonogenicity in vitro.
- These drugs induced apoptosis in FPA cells in a dose-dependent manner.
- Abnormal expression of cFos, WNT5A, NCAM1, JUP, AKT3, and ADCY1 was observed in FPA cells.
Conclusions:
- T5224, RSPO2, and AZD5363 demonstrate significant therapeutic potential for functioning pituitary adenoma.
- The identified genes (cFos, WNT5A, NCAM1, JUP, AKT3, ADCY1) represent potential prognostic and therapeutic targets for FPA.
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