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MI-773, a breaker of the MDM2/p53 axis, exhibits anticancer effects in neuroblastoma via downregulation of INSM1.
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; Lu, Jun; Hu, Shao-Yan; Li, Zhi-Heng; Pan, Jian.
Afiliación
  • Chen YL; School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Zhang ZM; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Li XL; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Tao YF; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Wu SY; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Fang F; Intensive Care Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Xie Y; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Liao XM; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Li G; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Wu D; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Wang HR; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Zuo R; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Cao HB; School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Pan JJ; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Yu JJ; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Zhang Z; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Chu XR; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Zhang YP; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Feng CX; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Wang JW; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Lu J; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Hu SY; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Li ZH; Department of Hematology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
  • Pan J; Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
Oncol Lett ; 22(6): 838, 2021 Dec.
Article en En | MEDLINE | ID: mdl-34712362
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncol Lett Año: 2021 Tipo del documento: Article Pais de publicación: Grecia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Oncol Lett Año: 2021 Tipo del documento: Article Pais de publicación: Grecia