Dopamine receptor D2S gene transfer improves the sensitivity of GH3 rat pituitary adenoma cells to bromocriptine.

Abstract

Bromocriptine, a dopamine agonist (DA), has been used in the treatment of prolactinomas. Recent studies have indicated that dopamine 2 receptor short isoform (D2S) may play an important role in suppressing PRL synthesis and prolactinoma cell growth under DA treatment. In the current study, we investigated the role of D2S in the therapeutic action of bromocriptine in GH3 using both in vitro and in vivo approaches. Infection of adenovirus-D2S increased D2S expression in GH3 cells (P<0.05). D2S expression significantly decreased the GH3 cell viability subjected to bromocriptine treatment in vitro (P<0.05). In nude mice, adenovirus-D2S transfection sensitized GH3 xenograft to bromocriptine treatment evidenced by the significant inhibition of D2S expressed tumor growth as compared with vector control. Furthermore, decrease of Bcl-2 expression, increase of Bax, and active Caspase-3 were found in D2S expressed GH3 xenograft subjected to bromocriptine treatment. In summary, our study indicates that D2S expression plays a critical role in the therapeutic action of bromocriptine in pituitary adenomas and that adenovirus-mediated D2S gene transfer combined with bromocriptine may provide a novel treatment for DA-resistant prolactinomas.

• Authors: Qiang Li, Zhipeng Su, Jie Liu, Lin Cai, Jianglong Lu, Shaojian Lin, Zhengkun Xiong, Weiqiang Li, Weiming Zheng, Jinsen Wu, Qichuan Zhuge, Zhebao Wu
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 382 Issue 1 Pg. 377-384 (Jan 25 2014) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 24184771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Receptors, Dopamine D2
• dopamine D2L receptor
• enhanced green fluorescent protein
• Green Fluorescent Proteins
• Bromocriptine

Topics

• Adenoma (drug therapy, pathology, ultrastructure)
• Adenoviridae (metabolism)
• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Bromocriptine (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Female
• Gene Transfer Techniques
• Green Fluorescent Proteins (metabolism)
• Mice
• Mice, Nude
• Pituitary Neoplasms (drug therapy, pathology, ultrastructure)
• Rats
• Receptors, Dopamine D2 (genetics, therapeutic use)
• Transduction, Genetic
• Transfection
• Xenograft Model Antitumor Assays