Title

 

Authors

E. Bergantin¹, C. Quarta², C. Nanni², S. Fanti², A. Pession¹ , G. Cantelli-Forti³ , P. Hrelia³ , R. Tonelli^3
 
1Dept of Pediatric Oncology and Emathology “Lalla Seràgnoli”, S.Orsola Hospital, University of Bologna, Italy
²Dept of Nuclear Medicine, S.Orsola Hospital, University of Bologna, Italy
³Dept of Pharmacology, University of Bologna, Italy
 

 

Abstract

Rhadbomyosarcoma (RMS) is the most common soft tissue sarcoma. Of the two main subtypes of RMS, alveolar (ARMS) and embryonal (ERMS), the alveolar one is associated with a worse prognosis and is characterized by translocations involving fusion proteins PAX3-FKHR and PAX7-FKHR (Sorensen et al., 2002). Sulforaphane (SFN), initially discovered as an activator of phase 2 enzymes, is an isothiocyanate that plays an important role as an anticancer agent that interacts and modulates several critical cellular targets in the tumorigenic process (Thejass et al., 2006). In this study, a mouse model of ARMS was set up for the preclinical evaluation of SFN, TRAIL and their combination effect. The microPET was used to monitor in real time the tumor growth and the response to treatment by the use of TBR (Dandekar et al., 2007). The in vivo analysis was conducted on xenograft mice inoculated s.c. with 10 million rhabdomyosarcoma alveolar cells and treated i.p. for 21 consecutive days with saline (control group), with SFN (treated group) and SFN + TRAIL at two scalar concentrations (group treated in combination). The TBR was calculated at regular intervals of seven days for the duration of treatment. The positivity of the inoculated cells was seen by the micro-PET after only two days after injection. The SFN alone resulted in a reduction of tumor growth, as well as TRAIL at the highest concentration but the combination of the same concentration of TRAIL with SFN showed instead the disappearance of the signal in micro-PET, leading the value of TBR under the threshold of positivity. The micro-PET is an useful tool through which it is possible to study the ongoing growth of tumor in mouse models, to decide the time of treatment and to monitor, in real time, the effect of potential drugs or the antitumor activity of molecules corresponding to the decrease of TBR. The promising results obtained by the combination of SFN with TRAIL represent the bases for future association studies in which the SFN could be used not only as an anticancer agent but also as a potential chemio-preventive agent.