Surgical resection coupled with
adjuvant radiotherapy and/or
doxorubicin based
chemotherapy are the mainstays of
synovial sarcoma (SS) treatment. Although effective as a SS adjuvant, the proposed mechanism of action of
doxorubicin remains controversial. Current opinion supports DNA damage-induced apoptosis. This in vitro study used
cDNA gene expression profiling to investigate whether apoptosis, alone or in combination with cell senescence, is induced by
doxorubicin in SS cells. Cell cultures of the FU-SY-1 SS, the pleomorphic SW982
sarcoma, and a primary dermal fibroblast (NHDF), were exposed to 500 nM
doxorubicin, and then processed for
cDNA microarray analysis. The one class response option of SAM (Significance Analysis of Microarrays) was used to test for significant overexpression of 15 apoptosis-related genes and nine senescence-related genes.
Drug-induced cell senescence was quantified by measuring
beta-galactosidase activity. None of 15 apoptosis-related genes and only two of nine senescence-related genes were identified by SAM as significantly overexpressed in
doxorubicin-treated cultures.
Drug-induced senescence as reflected by
beta-galactosidase activity was significantly increased (p < 0.05) only in FU-SY-1 SS cultures. Apoptosis does not appear to be a major determinant of
doxorubicin-induced mortality in FU-SY-1 SS or NHDF cultures, but may impact SW982 cells via the overexpression of BAX relative to Bcl-2.
Doxorubicin-induced cell senescence was prominent in FU-SY-1 SS cultures, but negligible in SW982 and NHDF cultures. Likely, both apoptosis and cell senescence contribute to
doxorubicin-induced cell death in this
synovial sarcoma cell line.