Tamoxifen Exerts Anticancer Effects on Pituitary Adenoma Progression via Inducing Cell Apoptosis and Inhibiting Cell...

Area of Science:

• Endocrinology
• Oncology
• Immunology

Background:

• Pituitary adenomas (PAs), though benign, cause significant complications like cardiovascular disease and metabolic dysfunction.
• Genomic analysis identified STAT6 as a potential therapeutic target in PAs.

Purpose of the Study:

• To investigate the efficacy of repositioning tamoxifen, an FDA-approved immune regulator, as a targeted therapy for pituitary adenomas.
• To elucidate the molecular mechanisms underlying tamoxifen's action on PA cells and tumor-associated macrophages.

Main Methods:

• Genomic analysis to identify STAT6 as a target.
• In vitro studies using GH3 and AtT-20 cells to assess tamoxifen's effects on proliferation, apoptosis, and molecular markers (p-PI3K, p-AKT, Bcl-2, p53, Bax).
• In vivo studies using pituitary adenoma xenografts in nude mice to evaluate tamoxifen's therapeutic effect.

Main Results:

• Tamoxifen inhibited PA cell proliferation (IC50 values 9.15 and 7.52 μM) and increased apoptosis in a dose-dependent manner.
• Tamoxifen downregulated key pro-survival proteins (p-PI3K, p-AKT, Bcl-2) and upregulated pro-apoptotic proteins (p53, Bax).
• Tamoxifen suppressed PA cell migration by reprogramming tumor-associated macrophages to the M1 phenotype via STAT6 and SHP1/SHP inhibition, and reduced tumor xenograft growth.

Conclusions:

• Tamoxifen demonstrates significant anti-tumor activity against pituitary adenomas through multiple molecular pathways.
• Tamoxifen's ability to modulate the tumor microenvironment by reprogramming macrophages adds to its therapeutic potential.
• Tamoxifen is a promising candidate for combination therapy in pituitary adenomas, meriting further clinical investigation.