MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells

Matteo Cassandri, Silvia Pomella, Alessandra Rossetti, Francesco Petragnano, Luisa Milazzo, Francesca Vulcano, Simona Camero, Silvia Codenotti, Francesca Cicchetti, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina, Alessandro Fanzani, Francesca Megiorni, Marialuigia Catanoso, Cinzia Marchese, Vincenzo Tombolini, Franco Locatelli, Rossella Rota, Francesco Marampon

Research output: Contribution to journalArticlepeer-review


Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. About 25% of RMS expresses fusion oncoproteins such as PAX3/PAX7-FOXO1 (fusion-positive, FP) while fusion-negative (FN)-RMS harbors RAS mutations. Radiotherapy (RT) plays a crucial role in local control but metastatic RMS is often radio-resistant. HDAC inhibitors (HDACi) radio-sensitize different cancer cells types. Thus, we evaluated MS-275 (Entinostat), a Class I and IV HDACi, in combination with RT on RMS cells in vitro and in vivo. MS-275 reversibly hampered cell survival in vitro in FN-RMS RD (RASmut) and irreversibly in FP-RMS RH30 cell lines down-regulating cyclin A, B, and D1, up-regulating p21 and p27 and reducing ERKs activity, and c-Myc expression in RD and PI3K/Akt/mTOR activity and N-Myc expression in RH30 cells. Further, MS-275 and RT combination reduced colony formation ability of RH30 cells. In both cell lines, co-treatment increased DNA damage repair inhibition and reactive oxygen species formation, down-regulated NRF2, SOD, CAT and GPx4 anti-oxidant genes and improved RT ability to induce G2 growth arrest. MS-275 inhibited in vivo growth of RH30 cells and completely prevented the growth of RT-unresponsive RH30 xenografts when combined with radiation. Thus, MS-275 could be considered as a radio-sensitizing agent for the treatment of intrinsically radio-resistant PAX3-FOXO1 RMS.

Original languageEnglish
JournalInternational journal of molecular sciences
Issue number19
Publication statusPublished - Oct 1 2021


  • Animals
  • Apoptosis/drug effects
  • Benzamides/pharmacology
  • Cell Cycle Checkpoints/drug effects
  • Cell Line, Tumor
  • Cell Proliferation/drug effects
  • DNA Damage/drug effects
  • DNA Repair/drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Mice
  • Oncogene Proteins, Fusion/genetics
  • Paired Box Transcription Factors/genetics
  • Pyridines/pharmacology
  • Radiation Tolerance/drug effects
  • Radiation-Sensitizing Agents/pharmacology
  • Rhabdomyosarcoma/genetics


Dive into the research topics of 'MS-275 (Entinostat) Promotes Radio-Sensitivity in PAX3-FOXO1 Rhabdomyosarcoma Cells'. Together they form a unique fingerprint.

Cite this