Fig. 4

In vivo antitumor effects of a third-generation SMI (MO-I-1182) targeting ASPH enzymatic activity on PDX murine models of human PDAC. a Histopathologic characteristics (H&E) of original tumors (F0) derived from PDAC patient B and xenografted tumors in representative mice of F1 through F4 generation PDX model. b Pulmonary macro-metastases in representative F4 PDX mice derived from patient B. One hundred percent (14/14) of F4 PDX mice had spontaneously developed pulmonary metastasis. c Expression profiling of ASPH-SRC components in resected primary PDAC tumor specimens derived from patients B. d Gross appearance of the involved lungs, histopathologic characteristics, and expression profiling of ASPH in transplanted primary tumors as well as pulmonary macro-metastases in a representative mouse of the F5 generation PDX model derived from PDAC patient B. e Transplanted primary tumor growth in mice of the F5 generation PDX model in response to i.p. injected SMI vs. DMSO control. It took 4–5 weeks for the transplanted tumors to grow up to 100 mm³, when treatment with MO-I-1182 (10 mg/kg, i.p., every other day) was initiated. The mice were followed up for 5 weeks until the tumors grew up to 1000 mm³. f Antitumor effects of i.p. injected SMI on pulmonary metastasis. SMI blocks pulmonary micro-/macro-metastases in mice of F5 generation PDX derived from patient B. g–i Expression profiling of ASPH and MMPs detected by IHC and qRT-PCR in representative mice of the F5 generation PDX model treated with SMI vs. DMSO control. ^*p < 0.05; ^**p < 0.01; ^***p < 0.001