Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas.
Brusatol Inhibits Tumor Growth and Increases the Efficacy of Cabergoline against Pituitary Adenomas.
复制标题
布鲁萨醇抑制肿瘤生长并提高卡麦角林抗垂体腺瘤的功效
DOI：
10.1155/2021/6696015
复制
发表时间：
2021
影响因子：
--
通讯作者：
Su Z
中科院分区：
文献类型：
--
作者：
Wu Z;Xu Y;Xu J;Lu J;Cai L;Li Q;Wang C;Su Z
卡麦角林(CAB)是治疗催乳素瘤的首选药物，也是最常见的垂体腺瘤亚型。然而，对其他类型的垂体瘤的耐药性和缺乏有效性仍然是这种治疗的临床挑战。已知布鲁塞尔醇(BT)可抑制多种癌细胞的生长并促进其凋亡。在我们目前的研究中，我们研究了Bt在体外和体内对垂体瘤细胞增殖的影响。Bt诱导大鼠和人垂体瘤细胞Annexin V表达增加，促进细胞凋亡相关蛋白的表达。对这种作用机制的研究表明，Bt增加了ROS的产生，并抑制了4EBP1和S6K1的磷酸化。此外，在裸鼠和垂体肿瘤细胞中，BT和CAB的联合治疗比单独治疗产生更大的抗肿瘤效果。总之，我们的结果表明，Bt诱导的ROS积聚和mTORC1信号通路的抑制导致了对肿瘤生长的抑制。联合应用CAB和Bt可提高治疗人垂体腺瘤的临床疗效。
Cabergoline (CAB) is the first choice for treatment of prolactinoma and the most common subtype of pituitary adenoma. However, drug resistance and lack of effectiveness in other pituitary tumor types remain clinical challenges to this treatment. Brusatol (BT) is known to inhibit cell growth and promote apoptosis in a variety of cancer cells. In our present studies, we investigate the effects of BT on pituitary tumor cell proliferation in vitro and in vivo. BT treatment resulted in an increase in Annexin V-expressing cells and promoted the expression of apoptosis-related proteins in rat and human pituitary tumor cells. Investigation of the mechanism underlying this effect revealed that BT increased the production of reactive oxygen species (ROS) and inhibited the phosphorylation of 4EBP1 and S6K1. Furthermore, treatment with a combination of BT and CAB resulted in greater antitumor effects than either treatment alone in nude mice and pituitary tumor cells. Collectively, our results suggest that the BT-induced ROS accumulation and inhibition of mTORC1 signaling pathway leads to inhibition of tumor growth. Combined use of CAB and BT may increase the clinical effectiveness of treatment for human pituitary adenomas.
登录
查看更多内容
影响因子：
5.8
作者：
Lin, Shao Jian;Wu, Ze Rui;Wu, Zhe Bao
通讯作者：
Wu, Zhe Bao
影响因子：
4.6
作者：
Harder B;Tian W;La Clair JJ;Tan AC;Ooi A;Chapman E;Zhang DD
通讯作者：
Zhang DD
影响因子：
3
作者：
Guo, Songbin;Zhang, Jinling;Zhang, Zhenfeng
通讯作者：
Zhang, Zhenfeng
影响因子：
7.5
作者：
Cai, Sabrina J.;Liu, Yang;Yang, Chunzhang
通讯作者：
Yang, Chunzhang
影响因子：
5.5
作者：
Lee, Jong Hyun;Rangappa, Shobith;Ahn, Kwang Seok
通讯作者：
Ahn, Kwang Seok