Open AccessMetformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts
Author(s) -
Gao Jun,
Liu Yang,
Han Gaijing,
Deng Kan,
Liu Xiaohai,
Bao Xinjie,
Feng Ming,
Yao Yong,
Lian Wei,
Xing Bing,
Lv Xiang,
Wang Renzhi
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13963
Subject(s) - ampk , prolactin , endocrinology , medicine , prolactinoma , bromocriptine , secretion , protein kinase a , metformin , chemistry , agonist , kinase , cancer research , receptor , biology , microbiology and biotechnology , diabetes mellitus , hormone
Metformin ( MET ) is a diabetes drug that activates AMP ‐activated protein kinase ( AMPK ), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma ( PRL oma), with particular respect to MET and bromocriptine ( BC ) as a PRL oma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor ( ER ) expression in both BC ‐sensitive and ‐resistant PRL oma samples; effects of the AMPK agonist MET (alone or with BC ) on in vitro proliferation and apoptosis, xenograft growth and prolactin ( PRL ) secretion of BC ‐sensitive and ‐resistant cells, and ER expression in xenografts. S ome BC ‐resistant PRL omas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRL oma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down‐regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down‐regulates ER α and ER β, and suppresses PRL oma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRL omas.