(P 131) GLUCOSE TRANSPORTER 1 (GLUT1) INHIBITION DECREASES THE GROWTH AND PROLIFERATION OF CHONDROSARCOMA

Objective: The glucose transporter 1 (GLUT1) is upregulated in many cancer cells, facilitating increased glucose uptake and fueling rapid cell growth and proliferation, making it a potential therapeutic target. However, the expression and function of GLUT1 in chondrosarcoma remain unknown. We investigated the expression and function of GLUT1 in chondrosarcoma, with subsequent analysis of the therapeutic value of targeted GLUT1 in chondrosarcoma.

Methods: Immunohistochemistry was performed to evaluate GLUT1 expression on a chondrosarcoma tissue microarray. GLUT1 expression in three chondrosarcoma cell lines and patient tissues was evaluated by Western blot and immunofluorescence assay. GLUT1 siRNA and GLUT1 inhibitor BAY876 were applied to assess the effect of GLUT1 inhibition on chondrosarcoma cell growth, proliferation, and apoptosis. The effect of GLUT1 inhibition on clonogenicity and cell motility were examined using 2D clonogenic and wound healing migration assays. An ex vivo 3D cell culture model was performed to mimic the in vivo chondrosarcoma environment and to assess how GLUT1 inhibition affects the capacity of chondrosarcoma cells to form characteristic spheroids.

Results: Immunohistochemistry showed GLUT1 is expressed in both chondrosarcoma tumor tissues and cell lines. Silencing of GLUT1 with siRNA and reduction of GLUT1 signaling with the GLUT1 inhibitor BAY876 decreased chondrosarcoma cell growth and proliferation, while also inducing cell death in a time- and dose-dependent manner. Inhibition of GLUT1 makes chondrosarcoma cells more sensitive to doxorubicin. Targeting GLUT1 also reduced chondrosarcoma cell clonogenicity formation and spheroid growth.

Conclusion: Our study showed GLUT1 is expressed in chondrosarcoma, and, when inhibited, causes chondrosarcoma cell growth and proliferation to decrease. These results support GLUT1 as a potential target in chondrosarcoma therapy.