title: 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.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Neurosurgery, Ningbo No. 2 Hospital, Ningbo 315000, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jianglong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shaojian
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jinsen
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: wyyyzhuge@gmail.com.
authors.forename: Qichuan
authors.initials: Q
authors.lastname: Zhuge
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: zhebaowu@aliyun.com.
authors.forename: Zhebao
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001971:Bromocriptine / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000627:therapeutic use*; D014161:Transduction, Genetic; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D017448:Receptors, Dopamine D2; C113776:dopamine D2L receptor; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D001971:Bromocriptine
keywords: Ad; Apoptosis; BRC; Bromocriptine; D2R; D2S; DA; Dopamine 2 receptor; Dopamine 2 receptor short isoform; GH3 cell; PRL; Pituitary adenoma; adenovirus; bromocriptine; dopamine 2 receptor; dopamine 2 receptor short isoform; dopamine agonist; prolactin