The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma
文献类型：期刊论文
| 作者 | Ji, Chenxing3,4; Xu, Wen5; Ding, Hong6,7 ; Chen, Zhengyuan3,4; Shi, Chengzhang3,4; Han, Jie7; Yu, Liang7; Qiao, Nidan3,4,8; Zhang, Yichao3,4,8; Cao, Xiaoyun3,4,8
|
| 刊名 | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
 |
| 出版日期 | 2022-03-05 |
| 页码 | 10 |
| ISSN号 | 0021-972X |
| 关键词 | p300 A-485 growth hormone pituitary adenoma |
| DOI | 10.1210/clinem/dgac128 |
| 通讯作者 | Li, Zhiyu(zhiyuli@cpu.edu.cn) ; Zhou, Bing(zhoubing@simm.ac.cn) ; Ye, Zhao(yezhaozj663812@126.com) |
| 英文摘要 | Context Growth hormone pituitary adenoma (GHPA), a major subtype of pituitary adenoma (PA), can lead to progressive somatic disfigurement, multiple complications, and even increased mortality. The efficacy of current treatments is limited; thus, a novel pharmacological treatment is urgently needed. As a histone acetyltransferase (HAT) coactivator, p300 can regulate the transcription of several genes that are crucial for PA tumorigenesis and progression. However, the role of p300 and its catalytic inhibitor in GHPA is still unclear. Objective We aimed to identify the expression of p300 in GHPA and in normal pituitary glands. Methods The expression of p300 was detected in GHPA and normal pituitary tissues. Genetic knockdown was performed by siRNA. The efficacy of the p300 inhibitor A-485 in the cell cycle, proliferation, apoptosis, and hormone secretion was investigated by flow cytometry, ELISAs, Western blotting, and qRT-PCR. RNA sequencing, bioinformatic analysis, and subsequent validation experiments were performed to reveal the potential biological mechanism of A-485. Results High expression of p300 was found in GHPA tissues compared with normal pituitary tissues. Knockdown of p300 inhibited cell proliferation and clone formation. Treatment with A-485 suppressed cell growth and inhibited the secretion of GH in vitro and in vivo. Further mechanistic studies showed that A-485 could downregulate the expression or activity of several oncogenes, such as genes in the Pttg1, c-Myc, cAMP and PI3K/AKT/mTOR signaling pathways, which are crucial for PA tumorigenesis and progression. Conclusion Our findings demonstrate that inhibition of HAT p300 by its selective inhibitor A-485 is a promising therapy for GHPA. |
| WOS关键词 | TRANSSPHENOIDAL SURGERY ; PI3K/AKT/MTOR PATHWAY ; SOMATOSTATIN ANALOGS ; TERM EFFICACY ; C-MYC ; GENE ; EXPRESSION ; CBP ; NATIONWIDE ; MORTALITY |
| 资助项目 | Ministry of Science and Technology of China (National Key R&D Program of China)[2017YFB0202600] ; Personalized Medicines Molecular Signature-based Drug Discovery and Development (Strategic Priority Research Program of the Chinese Academy of Sciences)[XDA12020368] ; National Natural Science Foundation of China[81802496] ; Shanghai Sailing Program[18YF1402700] ; China Pituitary Adenoma Specialist Council ; National High Technology Research and Development Program of China[2014AA020611] ; Chang Jiang Scholars Program ; National Program for Support of Top-Notch Young Professionals ; National Science Fund for Distinguished Young Scholars[81725011] |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| 出版者 | ENDOCRINE SOC |
| WOS记录号 | WOS:000785774200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299782]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Zhiyu; Zhou, Bing; Ye, Zhao |
| 作者单位 | 1.Fudan Univ, State Key Lab Med Neurobiol, Inst Brain Sci, Shanghai, Peoples R China 2.Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai 200040, Peoples R China 3.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Natl Ctr Neurol Disorders,Dept Neurosurg, 958 Jin Guang Rd, Shanghai 200040, Peoples R China 4.Fudan Univ, Neurosurg Inst, Shanghai 200040, Peoples R China 5.Fudan Univ, Hosp & Inst Obstet & Gynecol, Shanghai 200011, Peoples R China 6.China Pharmaceut Univ, Dept Med Chem, 639 Long Mian Ave, Nanjing 211198, Peoples R China 7.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China 8.Shanghai Key Lab Brain Funct Restorat & Neural Re, Shanghai 200040, Peoples R China 9.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Pathol, Shanghai 200040, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ji, Chenxing,Xu, Wen,Ding, Hong,et al. The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma[J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,2022:10. |
| APA | Ji, Chenxing.,Xu, Wen.,Ding, Hong.,Chen, Zhengyuan.,Shi, Chengzhang.,...&Zhao, Yao.(2022).The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma.JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,10. |
| MLA | Ji, Chenxing,et al."The p300 Inhibitor A-485 Exerts Antitumor Activity in Growth Hormone Pituitary Adenoma".JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2022):10. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。