Mesenchymal chondrosarcomas are rare and highly aggressive
sarcomas occurring in bone and soft tissue, with poor overall survival. Bcl-2 expression was previously shown to be upregulated in
mesenchymal chondrosarcomas. We here report on a newly derived
mesenchymal chondrosarcoma cell line, MCS170, in which we investigated treatment with the BH3 mimetic
ABT-737 alone or in combination with conventional
chemotherapy as a possible new therapeutic strategy. The presence of the characteristic HEY1-NCOA2 fusion was confirmed in the MCS170 cell line using FISH, RT-PCR, and sequencing. The MCS170 cell line was treated with
ABT-737 alone or in combination with
doxorubicin or
cisplatin. Cell viability and proliferation was determined using WST-1 viability assays and the xCELLigence system. Expression of Bcl-2 family members was studied using immunohistochemistry. Apoptosis was determined using the
caspase-glo 3/7 assay and western blot for PARP cleavage. The MCS170 cell line was sensitive to
doxorubicin treatment with an IC50 of 0.09 μM after 72 h, but more resistant to
cisplatin treatment with an IC50 of 4.5 μM after 72 h. Cells showed little sensitivity toward
ABT-737 with an IC50 of 1.8 μM after 72 h. Combination treatments demonstrated
ABT-737 synergism with
cisplatin as well as
doxorubicin as shown by induction of apoptosis and reduction in cell proliferation. Restoration of the apoptotic machinery by inhibition of Bcl-2 family members sensitizes MCS170
mesenchymal chondrosarcoma cells to conventional
chemotherapy. This indicates that combining the inhibition of Bcl-2 family members with conventional
chemotherapy can be a possible therapeutic strategy for patients with
mesenchymal chondrosarcoma.