Fig. 2.

K-80003 can enhance the sensitivity of some AG-resistant PDAC patients to AG chemotherapy. A, Method used to apply different treatments to PDO-AGR in vitro and quantitation of PDO fluorescence. Method used for corresponding PDOX treatments in vivo. B-F, Representative images of different PDO-AGRs that received different treatments. PDOs in each group treated for 48 h with saline or AG (Nab-paclitaxel 10nM plus GEM 30nM) or K-80003 (5 nM) or AG (Nab-paclitaxel 10nM plus GEM 30nM plus K-80003 5 nM). Live cells stained with calcein-AM (green), and dead cells with ethidium-1 (red). Quantitative data are shown on the right. Tumors from different groups of PDOXs received different treatments from weeks 2 after orthotopic xenograft injection of 1 million corresponding PDOs. Mice were treated with saline, K-80003 (20 mg/kg, twice weekly; bule arrows), the dual combination of gemcitabine (25 mg/kg, weekly), and nab-paclitaxel (15 mg/kg, weekly; red arrows), or the triple combination of gemcitabine and nab-paclitaxel (as dosed for the monotherapies) plus K-80003 for 3 weeks. Tumors were harvest at 3 weeks after injection. Fluorescence of tumors from mice in the different groups (5 mice per group). Survival curves for mice that received different treatments (5 mice per group). Not significant (ns), *P < 0.05; **P < 0.01; ***P < 0.001