We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1.
- Authors
Chen, Yan-Ling; Zhang, Zi-Mu; Li, Xiao-Lu; Tao, Yan-Fang; Wu, Shui-Yan; Fang, Fang; Xie, Yi; Liao, Xin-Mei; Li, Gen; Wu, Di; Wang, Hai-Rong; Zuo, Ran; Cao, Hai-Bo; Pan, Jing-Jing; Yu, Juan-Juan; Zhang, Zheng; Chu, Xin-Ran; Zhang, Yong-Ping; Feng, Chen-Xi; Wang, Jian-Wei
- Abstract
Neuroblastoma (NB) is a common pediatric malignancy associated with poor outcomes. Recent studies have shown that murine double minute2 homolog (MDM2) protein inhibitors are promising anticancer agents. MI-773 is a novel and specific antagonist of MDM2, however, the molecular mechanism of its anti-NB activity remains unclear. NB cell viability was measured by Cell Counting Kit-8 assay following MI-773 treatment. Cell cycle progression was analyzed using PI staining and apoptosis was assessed using Annexin V/PI staining. The molecular mechanisms by which MI-773 exerted its effects were investigated using a microarray. The results showed that disturbance of the MDM2/p53 axis by MI-773 resulted in potent suppression of proliferation, induction of apoptosis and cell cycle arrest in NB cells. In addition, microarray analysis showed that MI-773 led to significant downregulation of genes involved in the G2/M phase checkpoint and upregulation of hallmark gene associated with the p53 pathway. Meanwhile, knockdown of insulinoma-associated 1 decreased proliferation and increased apoptosis of NB cells. In conclusion, the present study demonstrated that MI-773 exhibited high selectivity and blockade affinity for the interaction between MDM2 and TP53 and may serve as a novel strategy for the treatment of NB.
- Subjects
ANTINEOPLASTIC agents; NEUROBLASTOMA; P53 antioncogene; DOWNREGULATION; CELL cycle
- Publication
Oncology Letters, 2021, Vol 22, Issue 6, pN.PAG
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2021.13099