{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:54:50Z","timestamp":1776873290683,"version":"3.51.2"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Applied Basic Research Program General of Shanxi Province","award":["201901D111430"],"award-info":[{"award-number":["201901D111430"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objective: Non-functioning pituitary neuroendocrine tumors (NF-PitNETs) represent a heterogeneous tumor type that lacks effective medical treatment. MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. In this study, we measured the expression levels and role of MDM2 in non-functioning PitNET patients\u2019 combined clinical features and investigated the effect of etoposide on the cell bioactivity of the GT1-1 cell line in vivo and in vitro. Methods: RT-PCR and immunochemistry measured the expression levels and role of MDM2 in 103 NF-PitNET patients\u2019 combined clinical features. Cell proliferation, migration, colony and apoptosis experiments measured the effect of etoposide on the GT1-1 cell line in vivo and in vitro. Results: There was more invasive behavior (p = 0.013) in patients with high MDM2, who were also younger (p = 0.007), were more frequently female (p = 0.049) and had larger tumor sizes (p = 0.018) compared with patients with low MDM2. Patients with high p53 were younger (p = 0.017) and had larger tumor sizes (p = 0.034) compared with patients with low p53. Univariate (p = 0.018) and multivariate (p = 0.023) Cox regression analysis showed that MDM2 was the independent factor for invasive behavior in NF-PitNET patients. Log-rank analysis showed that the average progression-free survival (PFS) time in the low MDM2 patients was longer than that in the high MDM2 patients (p = 0.044). Functional studies indicated that etoposide inhibited cell proliferation and cell migration and induced apoptosis in p53 independence in GT1-1 cells. Furthermore, etoposide significantly inhibited the growth of GT1-1-xenograft in BALB\/c nude mice. The tumor growth inhibition rate of etoposide was 67.4 \u00b1 4.6% after 14 d of treatment, which suggested the anti-tumor activity of etoposide. Conclusions: MDM2 played the role of tumorigenesis of NF-PitNET in a p53 independence manner, and an MDM2 inhibitor could be a potential choice for the treatment of NF-PitNET patients.<\/jats:p>","DOI":"10.3390\/medicina59020373","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T06:33:01Z","timestamp":1676442781000},"page":"373","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs"],"prefix":"10.3390","volume":"59","author":[{"given":"Xiaohui","family":"Yao","sequence":"first","affiliation":[{"name":"Shanxi Provincial People\u2019s Hospital, Taiyuan 030012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sida","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Central Nervous System Injury Research, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Cheng","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People\u2019s Hospital, Taiyuan 030012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gangli","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Provincial People\u2019s Hospital, Taiyuan 030012, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s11102-018-0865-7","article-title":"Management of NFAs: Medical treatment","volume":"21","author":"Greenman","year":"2018","journal-title":"Pituitary"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3171\/2018.7.GKS181589","article-title":"Hypopituitarism after Gamma Knife surgery for postoperative nonfunctioning pituitary adenoma","volume":"129","author":"Oh","year":"2018","journal-title":"J. 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