Research Paper Volume 14, Issue 8 pp 3597—3606

Synergistic blocking of RAS downstream signaling and epigenetic pathway in KRAS mutant pancreatic cancer

class="figure-viewer-img"

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). (CF) 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.