Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC)
Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC)
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黄体生成素释放激素 (GnRH) 受体作为三阴性乳腺癌 (TNBC) 的治疗靶点
DOI：
10.1007/s11523-014-0340-y
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发表时间：
2015
影响因子：
5.4
通讯作者：
Engel JB
中科院分区：
文献类型：
--
作者：
Kwok CW;Treeck O;Buchholz S;Seitz S;Ortmann O;Engel JB
在超过50%的病例中，三阴性乳腺癌表达促性腺激素释放激素（GnRH）受体，这可以用GnRH的肽类似物（如雷公藤松素）来靶向治疗。目前的研究是在体外三阴性乳腺癌（TNBC）模型中，研究雷普妥林作为单一疗法和联合化疗药物以及PI3K和ERK通路抑制剂的细胞毒活性。研究TNBC细胞株MDA-MB-231和HCC1806中GnRH受体的表达。用雷公霉素、化疗药物（顺铂、多西他赛、aez -112）、PI3K/AKT抑制剂（perifosine、aez -129）、ERK抑制剂（aez -134）和双重PI3K/ERK抑制剂aez -136作为单药治疗和联合治疗。MDA-MB-231和HCC1806 TNBC细胞均在信使(m)RNA和蛋白水平上表达GnRH受体，对雷公干扰素敏感，中位有效浓度（EC50）分别为31.21±0.21和58.50±19.50。雷普利林与顺铂联用时出现协同效应。在HCC1806细胞中，triptorelin与PI3K/AKT抑制剂perifosine和aez -129一起使用时，协同作用发生。在MDA-MB-231细胞中，雷普托雷林与ERK抑制剂aez -134和PI3K/ERK双抑制剂aez -136共同作用后，观察到协同作用。TNBC细胞上的GnRH受体可用于GnRH激动剂triptorelin靶向治疗这些癌症。在体外TNBC模型中，以雷普妥林、PI3K和ERK抑制剂以及化疗药物顺铂为基础的联合治疗具有协同作用。如果在体内得到证实，基于triptorelin和顺铂的临床试验可以很快进行，因为triptorelin是FDA批准的其他适应症，并且已知耐受性良好。
Triple negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH) in more than 50 % of the cases, which can be targeted with peptidic analogs of GnRH, such as triptorelin. The current study investigates cytotoxic activity of triptorelin as a monotherapy and in treatment combinations with chemotherapeutic agents and inhibitors of the PI3K and the ERK pathways in in vitro models of triple negative breast cancers (TNBC). GnRH receptor expression of TNBC cell lines MDA-MB-231 and HCC1806 was investigated. Cells were treated with triptorelin, chemotherapeutic agents (cisplatin, docetaxel, AEZS-112), PI3K/AKT inhibitors (perifosine, AEZS-129), an ERK inhibitor (AEZS-134), and dual PI3K/ERK inhibitor AEZS-136 applied as single agent therapies and in combinations. MDA-MB-231 and HCC1806 TNBC cells both expressed receptors for GnRH on messenger (m)RNA and protein level and were found sensitive to triptorelin with a respective median effective concentration (EC50) of 31.21 ± 0.21 and 58.50 ± 19.50. Synergistic effects occurred when triptorelin was combined with cisplatin. In HCC1806 cells, synergy occurred when triptorelin was applied with PI3K/AKT inhibitors perifosine and AEZS-129. In MDA-MB-231 cells, synergy was observed after co-treatment with triptorelin and ERK inhibitor AEZS-134 and dual PI3K/ERK inhibitor AEZS-136. GnRH receptors on TNBC cells can be used for targeted therapy of these cancers with GnRH agonist triptorelin. Treatment combinations based on triptorelin and PI3K and ERK inhibitors and chemotherapeutic agent cisplatin have synergistic effects in in vitro models of TNBC. If confirmed in vivo, clinical trials based on triptorelin and cisplatin could be quickly carried out, as triptorelin is FDA approved for other indications and known to be well tolerated.
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影响因子：
11.2
作者：
Joyce Bos
通讯作者：
Joyce Bos
LH-RH 类似物：I. 它们对生殖医学的影响。
DOI：
10.3109/09513599909167587
发表时间：
1999
期刊：
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
影响因子：
--
作者：
Schally,AV
通讯作者：
Schally,AV
影响因子：
45.3
作者：
Silver, Daniel P.;Richardson, Andrea L.;Garber, Judy E.
通讯作者：
Garber, Judy E.
影响因子：
2
作者：
Fister, Stefanie;Schlotawa, Lars;Gruendker, Carsten
通讯作者：
Gruendker, Carsten
LH-RH 类似物在卵巢癌中的主要治疗和挽救治疗。
DOI：
--
发表时间：
2000
期刊：
Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
影响因子：
--
作者：
G. Emons;K. Schulz
通讯作者：
K. Schulz