MAPK8 and cancer: Akt, Stat 3, JNK, and ERK1/2 signaling cascades are involved in the proliferation, migration, survival, angiogenesis, and lymphangiogenesis of various cancer cells.29–33 Thus, we evaluated the effects of the compounds on these signaling cascades and found that treatment of E12-1 or E13-1 combined with DOC caused a strong decrease in the expression of p-Stat 3 and p-Akt and a significant increase in the expression of p-JNK compared with treatment with the individual drugs alone.