Chondrosarcoma is a malignant cartilage-forming
cancer composed of cells derived from transformed cells that produce cartilage. Conventional
chemotherapy and
radiotherapy have very limited efficacy in patients with advanced
chondrosarcoma. In the present study, we reported a novel therapeutic approach in the treatment of
chondrosarcoma cells. We detected that
lactate dehydrogenase-A (LDHA) is highly active in
chondrosarcoma cells and
chondrosarcoma patient samples compared with normal chondrocyte cell lines and primary human chondrocyte. Moreover,
chondrosarcoma cells exhibited elevated levels of LDHA expression under
doxorubicin treatment. To further explore the mechanisms, we generated
doxorubicin-resistant cells from SW1353
chondrosarcoma cell line. Notably, the activity and expression of LDHA are upregulated in
doxorubicin-resistant cells. Moreover, our data showed a strong correlation between
glucose metabolism and
doxorubicin resistance in
chondrosarcoma cells;
doxorubicin-resistant cells displayed highly activated
glucose metabolism and depended more on
glucose supply. Finally, we reported a synergistic effect produced by incorporating
doxorubicin with glycolysis inhibitors-oxamate in the combined treatment of
chondrosarcoma cells in vitro and in vivo. In summary, the present study may aid in the development of new approaches using the combination of chemotherapeutic agents for the treatment of
chondrosarcoma patients.