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Role of HO‐1 in neuroblastoma resistance to Bortezomib
Author(s) -
Furfaro AnnaLisa,
Piras Sabrina,
Passalacqua Mario,
Domenicotti Cinzia,
Pronzato Maria Adelaide,
Marinari Umberto Maria,
Moretta Lorenzo,
Traverso Nicola,
Nitti Mariapaola
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1088.1
Subject(s) - bortezomib , neuroblastoma , pharmacology , cancer research , cancer cell , chemistry , cell culture , medicine , cancer , biology , immunology , multiple myeloma , genetics
Neuroblastoma (NB) is the most common solid tumor in childhood and is characterized by a poor prognosis due to the gain of a chemoresistant phenotype. Among the most recent anticancer therapies Bortezomib (BTZ) has shown impressive clinical activity to overcome cancer cell resistance to conventional therapy. The availability of antioxidants is recognized as one of the critical mechanisms in the development of cancer cell resistance and the up‐regulation of heme oxygenase‐1 (HO‐1) seems to play a key role. We analyzed the effects of BTZ on two different NB cell lines, SHSY‐5Y and HTLA‐230, well known respectively as sensitive and resistant to therapy, pointing out the role of HO‐1. SHSY‐5Y exposure to 5–40nM BTZ was able to strongly reduce cell proliferation while the same treatment was less effective on HTLA. Moreover, BTZ treatment was able to strongly up‐regulate HO‐1 in HTLA, while only a slight induction was observed in SHSY‐5Y. However, HO‐1 silencing was able to further decrease the proliferation rate of HTLA cells exposed to BTZ. In conclusion, we believe that proteasome inhibition could be a useful therapeutic approach against NB but the inhibition of HO‐1 should be considered in order to improve the effectiveness and prevent chemoresistance. Grants: PRIN2009M8FKBB_002 and Genoa University