Figure 6.

Proposed mechanism of pimozide in prolactinoma bromocriptine resistance. Pimozide inhibits the expression of STAT5, which suppresses cyclin D1 and Bcl-xL, resulting in reversal of bromocriptine resistance. PRL contributes to drug resistance through activation of the JAK2/STAT5 signaling pathway. Bromocriptine treatment alone increased STAT5 and Bcl-xL activation, and reduced cyclin D1 activity in prolactinoma cells. When combined with bromocriptine, pimozide suppressed activation of STAT5, which further decreased cyclin D1 and Bcl-xL expression. Further mechanistic studies are required for detailed characterization. The solid arrow represents a promoting effect, the red T symbol represents an inhibitory effect and the double headed arrow represents possible crosstalk between signaling. PRL, prolactin; PRLR, prolactin receptor; STAT5, signal transducer and activator of transcription 5A; Bcl-xL, B-cell lymphoma extra-large.