Targeted dual inhibition of c-Met/VEGFR2 signalling by foretinib improves antitumour effects of nanoparticle paclitaxel in gastric cancer models.

ABSTRACT: Elevated expression of multiple growth factors and receptors including c-Met and VEGFR has been reported in gastric adenocarcinoma (GAC) and thus provides a potentially useful therapeutic target. The therapeutic efficacy of foretinib, a c-Met/VEGFR2 inhibitor, was determined in combination with nanoparticle paclitaxel (NPT) in GAC. Animal studies were conducted in NOD/SCID mice in subcutaneous and peritoneal dissemination xenografts. The mechanism of action was assessed by Immunohistochemical and Immunoblot analyses. In c-Met overexpressing MKN-45 cell-derived xenografts, NPT and foretinib demonstrated inhibition in tumour growth, while NPT plus foretinib showed additive effects. In c-Met low-expressing SNU-1 or patient-derived xenografts, the foretinib effect was smaller, while NPT had a

SUBMITTER: Grojean M 

PROVIDER: S-EPMC8178268 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature