In vivo treatment of orthotopic pancreatic cancer with SDC1-Lip echinomycin. Mice were treated with Gemzar, echinomycin alone, or SDC1-Lip echinomycin weekly and survival was assessed. (A) In S2VP10 mice, echinomycin-only treatment was not significantly improved vs. Gemzar (p = 0.0923), while SDC1-Lip echinomycin treatment significantly improved survival compared to PBS (p = 0.00007), Gemzar (p = 0.0003), and echinomycin only (p = 0.0096). (B) In S2CP9 mice, SDC1-Lip echinomycin treatment significantly improved survival compared to PBS (p = 0.0018), Gemzar (p = 0.0017), and echinomycin only (p = 0.0073). (C) Cell lysates from pancreas tumor samples were evaluated for LC3-I, -II and pro- and cleaved caspase-3. Both echinomycin-treated and SDC1-Lip echinomycin-treated tumors shifted to LC3-II, but caspase-3 was not cleaved. (D) The ratio of LC3-II/I indicates that echinomycin and SDC1-Lip echinomycin resulted in autophagic flux increases. (E) The ratio of cleaved caspase-3/pro-caspase-3 indicates a lack of activation of apoptosis in echinomycin or SDC1-echinomycin-treated cells. Apoptosis was detected in Gemzar (apoptosis control)-treated cells. * p < 0.05.