Cancers, Vol. 16, Pages 853: Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma

Cancers, Vol. 16, Pages 853: Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma Cancers doi: 10.3390/cancers16050853 Authors: Silvia Codenotti Leonardo Sandrini Delia Mandracchia Luisa Lorenzi Giovanni Corsetti Maura Poli Michela Asperti Valentina Salvi Daniela Bosisio Eugenio Monti Stefania Mitola Luca Triggiani Michele Guescini Enrico Pozzo Maurilio Sampaolesi Stefano Gastaldello Matteo Cassandri Francesco Marampon Alessandro Fanzani Identifying the molecular mechanisms underlying radioresistance is a priority for the treatment of RMS, a myogenic tumor accounting for approximately 50% of all pediatric soft tissue sarcomas. We found that irradiation (IR) transiently increased phosphorylation of Akt1, Src, and Cav1 in human RD and RH30 lines. Synthetic inhibition of Akt1 and Src phosphorylation increased ROS levels in all RMS lines, promoting cellular radiosensitization. Accordingly, the elevated activation of the Akt1/Src/Cav1 pathway, as detected in two RD lines characterized by overexpression of a myristoylated Akt1 form (myrAkt1) or Cav1 (RDCav1), was correlated with reduced levels of ROS, higher expression of catalase, and increased radioresistance. We found that treatment with cholesterol-lowering drugs such as lovastatin and simvastatin promoted cell apoptosis in all RMS lines by reducing Akt1 and Cav1 levels and increasing intracellular ROS levels. Combining statins with I...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research