Decitabine modulates dopamine agonist sensitivity in gh3 rat pituitary tumor cells via Trim7

Pituitary prolactinoma is the most prevalent subtype of functional pituitary adenoma, for which dopamine agonists (DAs) have been established as the universal first-line therapeutic regimen in clinical practice. Approximately 10-25% of patients exhibit poor therapeutic responsiveness to DAs, presenting with persistent hyperprolactinemia and uncontrolled tumor growth, while the molecular mechanisms underlying this drug resistance phenotype remain incompletely characterized.

In the present study, GH3 rat pituitary tumor cells were employed as the in vitro experimental model to investigate whether the DNA methyltransferase inhibitor decitabine could modulate cellular sensitivity to dopamine agonists, and to further elucidate the associated potential molecular basis. Transcriptome sequencing coupled with systematic bioinformatics analysis was conducted on GH3 cells after decitabine intervention to screen candidate differentially expressed genes, from which Trim7 was selected as the key target for subsequent functional validation.

Functional assays demonstrated that Trim7 overexpression significantly enhanced cabergoline-induced apoptosis in GH3 cells. A concomitant reduction in cell proliferation was also observed in the Trim7 overexpression group compared with the empty vector control, although this difference did not reach statistical significance.

Collectively, these data establish a significant correlative relationship between Trim7 upregulation and improved dopamine agonist sensitivity in GH3 cells. Complementary loss-of-function experiments are still required to define the definitive causal role of Trim7 in this regulatory axis. The present findings provide preliminary evidence for the involvement of epigenetic regulation in dopamine agonist resistance, and suggest that Trim7 may serve as a promising potential therapeutic target for future intervention strategies in drug-resistant prolactinomas.