Figure - PMC

Skip to main content

View full-text article in PMC

. Author manuscript; available in PMC: 2023 Sep 1.

Published in final edited form as: Clin Cancer Res. 2022 Sep 1;28(17):3836–3849. doi: 10.1158/1078-0432.CCR-22-1052

Figure 6. — Changes in NCH-MN-1 xenografts with acquired resistance to trametinib. A, Mice bearing NCH-MN-1 tumors resistant to trametinib (cycle 3) were treated with trametinib (1 mg/kg daily for up to 5 days). B, Levels of DUSP6 in parental or trametinib resistant MN-1 xenografts. C, Cells from parental NCH-MN-1 xenografts, trametinib-resistant xenografts (TramR, cycle 3), or cells from NCH-MN-1 tumors treated for three cycles of trametinib—rapamycin (Trap). Trametinib-resistant cells show enhanced MAPK signaling. D, Response to increasing concentrations of trametinib in parental, trametinib-resistant, and cells isolated from tumors after three cycles of combination treatment. E, Response to trametinib of NCH-MN-1 cells from parental PDX tumor ( red line) and trametinib-resistant xenografts (■ black line). Cells cultured in stem cell medium supplemented with FGF and rEGF were exposed to indicated concentration of trametinib for 72 hours. Cell proliferation was measured by Alamar Blue. h, hours.

Inline graphic — Changes in NCH-MN-1 xenografts with acquired resistance to trametinib. A, Mice bearing NCH-MN-1 tumors resistant to trametinib (cycle 3) were treated with trametinib (1 mg/kg daily for up to 5 days). B, Levels of DUSP6 in parental or trametinib resistant MN-1 xenografts. C, Cells from parental NCH-MN-1 xenografts, trametinib-resistant xenografts (TramR, cycle 3), or cells from NCH-MN-1 tumors treated for three cycles of trametinib—rapamycin (Trap). Trametinib-resistant cells show enhanced MAPK signaling. D, Response to increasing concentrations of trametinib in parental, trametinib-resistant, and cells isolated from tumors after three cycles of combination treatment. E, Response to trametinib of NCH-MN-1 cells from parental PDX tumor ( red line) and trametinib-resistant xenografts (■ black line). Cells cultured in stem cell medium supplemented with FGF and rEGF were exposed to indicated concentration of trametinib for 72 hours. Cell proliferation was measured by Alamar Blue. h, hours.