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多巴胺受体亚型DRD2、DRD5在垂体瘤药物治疗中的作用

Role of dopamine receptor subtypes DRD2 and DRD5 in drug therapy of pituitary tumors

摘要:

目的 观察多巴胺5型受体(DRD5)、多巴胺2型受体(DRD2)在垂体瘤药物治疗中的作用,为垂体瘤药物治疗提供新策略.方法 通过免疫组织化学检测了上海瑞金医院及仁济医院收治的33例垂体瘤组织标本中DRD5、DRD2表达情况.通过原代细胞实验技术分离垂体瘤细胞,卡麦角林、DRD5激动剂(SKF38393)、DRD2激动剂(Quinypirol)作用于原代细胞,采取MTS法检测细胞活性,分析33例垂体瘤患者DRD5、DRD2表达和药物疗效的相互关系.结果 (1)免疫组化分析33例垂体瘤组织标本,泌乳素瘤17例、无功能腺瘤13例,生长素瘤3例.其中22例高表达DRD2(66.7%);24例高表达DRD5(72.7%).(2)卡麦角林50 μmol/L、喹吡罗50 μmol/L、SKF38393 25 μmol/L浓度作用于原代垂体瘤细胞;在33例原代细胞中,卡麦角林25例有效(75.8%),喹吡罗16例有效(48.5%),SKF38393有效15例(45.5%).(3)卡麦角林、喹吡罗、SKF38393对DRD2和DRD5均高表达的原代细胞有效率分别为78.6%、71.4%、50%,对DRD2高表达而DRD5低表达的原代细胞有效率分别为75%、62.5%、12.5%,对DRD2低表达而DRD5高表达的原代细胞有效率分别为80%、10%、70%,对DRD2低表达且DRD5低表达的原代细胞则无明显活性变化.结论 (1)垂体瘤中DRD2和DRD5均有比较丰富的表达量;(2)卡麦角林、DRD2激动剂、DRD5激动剂能效抑制垂体瘤的生长,其中以卡麦角林的有效率最高;(3)在缺乏DRD2的情况下,DRD5是另一个垂体瘤治疗的有效靶点.

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Objective To study the role of dopamine receptor subtype DRD2 and DRD5 in the treatment of pituitary adenoma,and toprovide a novel strategy for the drug-resistant pituitary adenomas.Methods Immunohistochemistry was used to detect the expression of dopamine type 5 receptor (DRD5) and dopamine type 2 receptor (DRD2) in 33 primary pituitary tumor tissue samples.Cabergoline,DRD5 agonist (SKF38393),and DRD2 agonist (Quinypirol) were used to treat primary pituitary tumor cells,and MTS was used to evaluate cell activity,in order to analyze the correlation between drug efficacy and the expression of DRD5 and/or DRD2 in 33 pituitary tumor.Results (1) Pathological analysis of 33 pituitary tμumor tissue samples indicated 17 cases of prolactinoma,13 cases of non-functional adenoma,3 cases of growth hormone (GH) tumor,among which 22 cases with high expression of DRD2 (66.7%) and 24 cases with high expression of DRD5 (72.7%).(2) Primary pituitary tumor cells were treated with Cabergoline at 50 μmol/L,Quinypirol at 50 μmol/L and SKF38393 at 25 μmol/L.Among the 33 primary cells,Cabergoline was effective in 25 cases (75.8%),Quinypirol in 16 cases (48.5%),and SKF38393 in 15 cases (45.5%).(3) The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with high expression of DRD2 and DRD5 were 78.6%,71.4% and 50% respectively.The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with high DRD2 expression and low DRD5 expression were 75%,62.5% and 12.5% respectively.The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with low DRD2 expression and high DRD5 expression were 80%,10% and 70% respectively.The efficiency of Cabergoline,Quinypirol and SKF38393 in the primary cell with low DRD2 and DRD5 expression had no significant activity change.Conclusion (1) Both DRD2 and DRD5 are highly expressed in pituitary tumors;(2) cabergoline,DRD2 agonist and DRD5 agonist effectively inhibit the growth of pituitary tumor,among which Cabergoline has the highest efficiency;(3) in the absence of DRD2,DRD5 is an alternative target to treat the pituitary tumors.

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