The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They effectively reduce tumor size, and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, but the mechanisms are still unknown. Thus, we investigated whether there are differences in drug sensitivity between CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC, and MMQ cells are more sensitive to CAB. And BRC and CAB showed different way to induce cell death: BRC induced prolactinoma cell death mainly in apoptosis, CAB induced pituitary prolactinoma cell death mainly autophagic cell death. After gene microarrays analysis, we found that BRC induces apoptosis of prolactinoma cells through ERK/EGR1 signaling pathway, whereas CAB induces autophagic death by inhibiting AKT/mTOR signaling pathway. Our study demonstrated for the first time the difference in drug sensitivity and differential mechanisms of BRC and CAB-treated prolactinoma cells, which will provide a theoretical basis for the accurate treatment of prolactinoma.
