Fig. 8

Pancreatic cancer CDXs with circ-MTHFD1L silencing is more sensitive to olaparib combined with gemcitabine therapy. A-D BALB/c nude mice (4–6 week-old males) were subcutaneously injected with stably transfected PANC-1-GR cells. Four weeks after implantation, the mice were treated with Gemcitabine (50 mg/kg/twice a week) by tail vein injection. Mice were sacrificed on week 8, and xenografts were isolated and measured. E-H BALB/c nude mice (4–6 week-old males) were subcutaneously injected with PANC-1-GR cells and treated with gemcitabine (50 mg/kg/twice a week) tail vein injection starting on week 4. Six weeks later, the most resistant xenograft was disaggregated and implanted subcutaneously into BALB/c nude mice (4–6 week-old males) as the second GR-CDX. Two weeks after implantation, the second GR-CDX generation mice were treated with sh-circ-MTHFD1L lentivirus (twice a week) and randomized into four groups on week 3. The four groups of mice were treated as follows: gemcitabine alone, olaparib alone, gemcitabine combined with olaparib, and negative control. Mice were sacrificed on week 6, and xenografts were isolated and measured. Data are shown as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001, between the indicated groups. I Schematic illustration of the circ-MTHFD1L/miR-615-3p/RPN6 axis in PDAC cells