Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine
Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine
复制标题
卡麦角林和氯喹联用抑制垂体瘤
DOI：
10.1210/jc.2017-00627
复制
发表时间：
2017-10-01
影响因子：
5.8
通讯作者：
Wu, Zhe Bao
中科院分区：
文献类型：
--
作者：
Lin, Shao Jian;Wu, Ze Rui;Wu, Zhe Bao
语境
多巴胺激动剂卡麦角林(CAB)已被广泛用于治疗催乳素瘤和其他类型的垂体腺瘤，但由于一些催乳素瘤患者对其不耐受以及对其他类型的垂体瘤缺乏疗效而阻碍了其临床应用。氯喹(CQ)是一种广泛用于治疗疟疾的古老药物。最近的研究，包括我们自己的研究，已经发现CAB和CQ参与了自噬的诱导和自噬细胞死亡的激活。
客观化
为了测试CAB和CQ是否可以协同作用抑制垂体腺瘤和其他癌症的生长。
结果
用大鼠垂体肿瘤细胞系MMQ和GH3、人垂体瘤细胞原代培养和几种人肿瘤细胞系进行的体外研究表明，CQ增强了CAB对细胞增殖的抑制作用。这些结果在裸鼠体内异种移植模型和雌激素诱导的大鼠催乳素瘤中得到证实。为了了解CAB和CQ联合作用的机制，我们建立了一个低CAB剂量的条件，在该条件下CAB能够诱导自噬，但不能抑制细胞生长。在低剂量CAB中加入CQ可阻断正常的自噬周期并诱导细胞凋亡，表现为p62/caspase-8/LC3-II的进一步积聚。
结论
这些数据表明，CAB和CQ的联合使用可能会提高治疗人类垂体腺瘤和其他癌症的临床有效性，使其成为肿瘤和癌症治疗的一个有吸引力的选择。
Context
The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death.
Objective
To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers.
Results
In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II.
Conclusion
The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.