Research Paper Volume 14, Issue 8 pp 3597—3606
Synergistic blocking of RAS downstream signaling and epigenetic pathway in KRAS mutant pancreatic cancer
Figure 3. Synergistic effects elicited by combined treatment trametinib and JQ1 in pancreatic cancer. (A) Effect of trametinib and/or JQ1 on the percentage of cells in relative trametinib-sensitive PDAC cell lines (AsPC-1 and PSN-1). Light gray bars show control values. ‘‘Multiplication’’ indicates the expected effect of combined treatment if single-agent effects were multiplied; the red arrow indicates the actual effect of the combination. (B) Effect of trametinib and/or JQ1 on the percentage of cells in relative trametinib-resistant PDAC cell lines (PANC-1 and CFPAC-1). (C–F) Combination index (CI) (top) and isobologram (bottom) analyses reveal the synergistic effect of trametinib and JQ1 not only in trametinib-sensitive PDAC cell lines (AsPC-1 and PSN-1), but also in trametinib-resistant PDAC cell lines (PANC-1 and CFPAC-1). Fraction affected (Fa)-CI plots (top) and normalized isobolograms (bottom) are shown.