PMID- 33890452 OWN - Quintessenz Verlags-GmbH CI - Copyright Quintessenz Verlags-GmbH OCI - Copyright Quintessenz Verlags-GmbH TA - Chin J Dent Res JT - Chinese Journal of Dental Research IS - 1867-5646 (Electronic) IS - 1462-6446 (Print) IP - 1 VI - 24 PST - ppublish DP - 2021 PG - 21-31 LA - en TI - Surviving Inhibition Induces Cell Cycle Arrest and Disrupts Multipotency in Haemangioma Stem Cells LID - 10.3290/j.cjdr.b1105869 [doi] FAU - Wang, Bei Ke AU - Wang B FAU - Li, Hui Min AU - Li H FAU - Yang, Jie Gang AU - Yang J FAU - Ren, Jian Gang AU - Ren J FAU - Cai, Yu AU - Cai Y FAU - Zhao, Ji Hong AU - Zhao J FAU - Zhao, Yi Fang AU - Zhao Y FAU - Jia, Jun AU - Jia J FAU - Zhang, Wei AU - Zhang W CN - OT - haemangioma stem cells OT - infantile haemangioma OT - survivin OT - YM155 AB - Objective: To explore the potential therapies for infantile haemangiomas by targeting survivin, a member of the inhibitor of apoptosis protein family, using its specific small molecule inhibitor YM155. Methods: The expression of survivin in human haemangioma tissue was explored using immunohistochemistry and immunohistofluorescence. Cell cycle analysis and EdU assays were used to measure cell proliferation. Heochst33342 and Annexin V/PI double staining were performed to measure cell apoptosis. The capacity for self-renewal and multilineage differentiation potential of haemangioma stem cells (HemSCs) were measured by clone formation assays and multiple differentiation assays. Murine haemangioma models were established to explore the therapeutic efficacy of YM155 in vivo. Results: Strong staining of survivin in stromal cells was observed in the proliferative haemangioma tissue. In vitro studies demonstrated that YM155 induced cell cycle arrest and proliferation suppression of HemSCs, and also caused cell apoptosis at a higher concentration. YM155 impaired the self-renewal capacities and damaged multiple differentiation potentials of HemSCs. Importantly, YM155 suppressed blood vessel formation and cell proliferation, and induced cell apoptosis in murine haemangioma models. Conclusion: The present study demonstrated that targeting survivin using its specific suppressant, YM155, prevented the progression of infantile haemangioma by suppressing cell proliferation, inducing cell apoptosis and disrupting the differentiation potential of HemSCs. These results indicate a novel and promising therapeutic approach for the treatment of infantile haemangioma. AID - 1105869