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 7. — Response of IC-3635 cells derived from trametinib-resistant xenografts. A, Cells were isolated from subcutaneous IC-3635 xenografts [cycle 4 trametinib (TramR) or cycle 4 combination treatment (Trap) treatment] and grown in serum-free conditions (left) or serum supplemented medium. In serum-free medium inhibition of MAPK and TORC1 signaling was similar in all derivatives, whereas in serum containing conditions of growth, inhibition of MAPK and TORC1 signaling was markedly attenuated only in cells derived from parental IC-3635 tumors and from combination treated tumors (Trap). B, IC-3635 trametinib-resistant cells were incubated with trametinib (2 nmol/L) in the absence or presence of receptor tyrosine kinase inhibitors. Phosphorylation of ERK1/2 and S6 were determined at 24 hours. C, Response of parental (▲) or IC-3635TramR (■ trametinib resistant) cells to trametinib without or with the panRAF inhibitor LY3009120 (). Cells were cultured in stem cell medium supplemented with FGF and EGF and exposed to the indicated concentration of trametinib with or without combining panRaf inhibitor for 72 hours. Cell viability was measured by Alamar Blue, untreated cells were set as 100%.

Inline graphic — Response of IC-3635 cells derived from trametinib-resistant xenografts. A, Cells were isolated from subcutaneous IC-3635 xenografts [cycle 4 trametinib (TramR) or cycle 4 combination treatment (Trap) treatment] and grown in serum-free conditions (left) or serum supplemented medium. In serum-free medium inhibition of MAPK and TORC1 signaling was similar in all derivatives, whereas in serum containing conditions of growth, inhibition of MAPK and TORC1 signaling was markedly attenuated only in cells derived from parental IC-3635 tumors and from combination treated tumors (Trap). B, IC-3635 trametinib-resistant cells were incubated with trametinib (2 nmol/L) in the absence or presence of receptor tyrosine kinase inhibitors. Phosphorylation of ERK1/2 and S6 were determined at 24 hours. C, Response of parental (▲) or IC-3635TramR (■ trametinib resistant) cells to trametinib without or with the panRAF inhibitor LY3009120 (). Cells were cultured in stem cell medium supplemented with FGF and EGF and exposed to the indicated concentration of trametinib with or without combining panRaf inhibitor for 72 hours. Cell viability was measured by Alamar Blue, untreated cells were set as 100%.