Abstract
Although pituitary adenomas are histologically benign, they are often accompanied by multiple complications, such as cardiovascular disease and metabolic dysfunction. In the present study, we repositioned the Food and Drug Administration -approved immune regulator tamoxifen to target STAT6 based on the genomics analysis of PAs. Tamoxifen inhibited the proliferation of GH3 and AtT-20 cells with respective IC50 values of 9.15 and 7.52 μM and increased their apoptotic rates in a dose-dependent manner. At the molecular level, tamoxifen downregulated phosphorylated PI3K, phosphorylated AKT and the anti-apoptotic protein Bcl-2 and increased the expression of pro-apoptotic proteins p53 and Bax in GH3 and AtT-20 cells. Furthermore, tamoxifen also inhibited the migration of both cell lines by reprogramming tumor-associated macrophages to the M1 phenotype through STAT6 inactivation and inhibition of the macrophage-specific immune checkpoint SHP1/SHP. Finally, administration of tamoxifen (20, 50, 100 mg·kg−1·d−1, for 21 days) inhibited the growth of pituitary adenomas xenografts in nude mice in a dose-dependent manner. Taken together, tamoxifen is likely to be a promising combination therapy for pituitary adenomas and should be investigated further.
Highlights
Published: 28 February 2022Pituitary adenoma (PA) is the second-most common intracranial neuroendocrine malignancy, accounting for about 15–25% of all intracranial neoplasms [1,2]
Pituitary Adenomas Progression Correlates with signal transducer and activator of transcription 6 (STAT6) Expression Levels
The mRNA expression levels of these hub genes were validated through qRT-PCR, which showed a positive correlation between the expression levels of STAT6 and the progression of PAs (Figure 3B), indicating STAT6 is a potential therapeutic target
Summary
Pituitary adenoma (PA) is the second-most common intracranial neuroendocrine malignancy, accounting for about 15–25% of all intracranial neoplasms [1,2]. PAs are histologically benign [3], hypersecretion of pituitary hormones from the tumor masses can result in multiple complications by acting in a paracrine manner. Cardiovascular diseases are the primary complications associated with PAs, which can trigger metabolic dysfunction and impair quality of life. 34–60% of the PAs are invasive [3], which makes surgical resection challenging and leads to high recurrence rates [4]. The benefits of chemotherapy and radiotherapy are minimal for PA patients [5–7]. The currently marketed drugs for PAs can only relieve some symptoms caused by abnormal hormone secretion, but cannot inhibit tumor growth, thereby warranting further drug development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
