Bromocriptine induces autophagy-dependent cell death in pituitary adenomas
10.3760/cma.j.issn.1671-8925.2017.03.008
- VernacularTitle:溴隐亭诱导垂体瘤自噬性细胞死亡的实验研究
- Author:
Xin GENG
1
;
Lixin MA
;
Hongpeng DU
;
Zhenzhu LI
;
Zefu LI
Author Information
1. 滨州医学院附属医院神经外科
- Keywords:
Autophagic cell death;
Bromocriptine;
Prolactinoma;
Cell cycle
- From:
Chinese Journal of Neuromedicine
2017;16(3):256-261
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the mechanism of bromocriptine (BRC) inducing autophagy-dependent cell death in pituitary adenomas and to explore its significance.Methods Thirty pituitary adenomas excised in our hospital from June 2013 to December 2015 were collected;the expressions of LC3 and Bcl-2 in these pituitary adenomas and normal brain tissues were examined by immunohistochemical staining.The rat hypophysoma MMQ cells were conventionally cultured in vitro;after 24 h of treatment with 60 μmol/L BRC,cytometry was performed to detect the variation of these cell cycle;the protein expressions of microtubule-associated protein light chain 3-Ⅰ (LC3-Ⅰ) and light chain 3-1Ⅱ (LC3-1Ⅱ) and the ratio of Bcl-2/Bax were measured by Western blotting after 24 h of treatment with various concentrations BRC (0,30 and 60 μ moi/L) for the MMQ cells.Results The LC3 protein expression rate in the pituitary adenomas was 80% (24/30) and that in the normal brain tissues was 0% (0/30);Bcl-2 protein expression rate in the pituitary adenomas was 83.33% (25/30) and that in the normal brain tissues was 0% (0/30).The high expression rates of LC3 and Bcl-2 in pituitary adenomas were significantly higher than those of the normal brain tissues (P<0.05).Patients with increased prolactin after BRC treatment had significantly higher expression rates of LC3 and Bcl-2 than those with decreased prolactin after BRC treatment (P<0.05).After treatment with 60 μmol/L BRC for 24 h,the number of MMQ cells in G0-G1 phase was significantly larger than controls (P<0.05).After 24 h of induction with various concentrations BRC,Western blotting showed that the conversion ratio of LC3-Ⅰ to LC3-Ⅱ in MMQ cells was significantly increased following the increase of BRC concentration (P<0.05);the ratio of Bcl-2 and Bax showed no significant difference among the 0,30 and 60 μ mol/L BRC treatment groups (P>0.05).Conclusion The death manner of BRC-treated pituitary adenoma cells is mainly autophagic cell death rather than apoptosis.