Fig. 6
AAV-mediated DAB2 knockdown inhibited tumour progression in human organoid model and PDX tumour mouse model. A Schematic diagram of the two mouse models: patient-derived organoids (PDO) model and patient-derived xenografts (PDX) model. B-D Parental PDO1#/2#/3# were digested into single cell suspensions and then seeded into 24-well plates. (The endogenous DAB2 expression is low in PDO1# but high in PDO2#/3#) Saline, AAV-null and AAV-shDAB2 were added into each group. Representative images of organoids in each group at day 1 (baseline) and day 7 (after treatment) were shown. The diamater of organoids was measured (***P < 0.001). E The expression of DAB2 and active-YAP1 in PDOs were analyzed by western blot after receiving the treatment of saline, AAV-null and AAV-shDAB2. F The expression of DAB2 and active-YAP1 in PDOs were analyzed by IF in DAB2low PDO1# and DAB2high PDO2#. Quantification of positive active-YAP1 cells was shown; **P < 0.01 (right panel). G-H PDX models from the patient1#/2# were randomized into three groups and then administrated with saline, AAV-null and AAV-shDAB2. The tumors were harvested on day 35. The expression of DAB2 and active-YAP1 in PDOs were analyzed by western blot after receiving the above treatment. The volume of PDXs was also measured (***P < 0.001). I) The expression of DAB2, active-YAP1, and Ki-67 were analyzed by IHC using paraffin-embedded tumor tissues from PDX mouse model