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Published on: May 6, 2018
Proteasomes are not a target for doxorubicin in feline injection-site sarcoma
F Cerruti1, M Martano, E Morello
1Department of Veterinary Morphophysiology, University of Turin, Grugliasco, Italy.
Abstract:
The potent anti-cancer agent doxorubicin (DOX) induces apoptosis of rapidly proliferating cells by inhibiting cellular proteasomes. The aim of the present study was to determine whether DOX modulates the level of expression and function of proteasomes in feline injection-site sarcoma (FISS). Tissue extracts from primary sarcoma lesions and the related healthy subcutis of 18 cats affected by FISS were investigated. Nine of these cats had received neoadjuvant DOX treatment and nine cats did not receive this therapy. There was enhanced proteasome expression in FISS, but this was not affected by administration of DOX. This finding may account for the low clinical effectiveness of DOX therapy in FISS and provides the rationale for developing new therapeutic protocols aimed at achieving better proteasomal inhibition in FISS and other tumours that respond poorly to DOX therapy.
Insights
Doxorubicin (DOX) cancer therapy did not alter proteasome levels in feline injection-site sarcoma (FISS). Enhanced proteasome expression in FISS may explain DOX
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- Doxorubicin (DOX) is a potent anti-cancer agent that induces apoptosis by inhibiting cellular proteasomes.
- Feline injection-site sarcoma (FISS) is a challenging cancer in cats.
- The role of proteasomes in FISS and their modulation by DOX is not well understood.
Purpose of the Study:
- To investigate the expression and function of proteasomes in FISS.
- To determine if DOX treatment affects proteasome levels in FISS.
- To understand the implications for DOX therapy effectiveness in FISS.
Main Methods:
- Analysis of tissue extracts from FISS lesions and healthy subcutis in 18 cats.
- Comparison between cats receiving neoadjuvant DOX and those not receiving therapy.
- Assessment of proteasome expression and function.
Main Results:
- Proteasome expression was enhanced in FISS compared to healthy tissue.
- DOX administration did not significantly affect proteasome expression levels in FISS.
- This suggests that existing proteasome levels in FISS are not modulated by DOX.
Conclusions:
- Enhanced proteasome expression in FISS may contribute to the limited clinical effectiveness of DOX therapy.
- New therapeutic strategies targeting improved proteasomal inhibition are needed for FISS.
- These findings provide a rationale for developing novel treatments for DOX-resistant tumors.
