2. Academic Validation
  3. MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1

MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1

  • Oncol Lett. 2021 Dec;22(6):838. doi: 10.3892/ol.2021.13099.
Yan-Ling Chen 1 2,  Zi-Mu Zhang 2,  Xiao-Lu Li 2,  Yan-Fang Tao 2,  Shui-Yan Wu 3,  Fang Fang 2,  Yi Xie 2,  Xin-Mei Liao 2,  Gen Li 2,  Di Wu 2,  Hai-Rong Wang 2,  Ran Zuo 1 2,  Hai-Bo Cao 2,  Jing-Jing Pan 2,  Juan-Juan Yu 2,  Zheng Zhang 2,  Xin-Ran Chu 2,  Yong-Ping Zhang 2,  Chen-Xi Feng 2,  Jian-Wei Wang 2,  Jun Lu 4,  Shao-Yan Hu 2 4,  Zhi-Heng Li 2,  Jian Pan 2
Affiliations

Affiliations

  • 1 School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • 2 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • 3 Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • 4 Department of Hematology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
PMID: 34712362 DOI: 10.3892/ol.2021.13099
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.

Keywords

MI-773; insulinoma-associated 1; murine double minute2 homolog; neuroblastoma; p53.

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