Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models.

ABSTRACT:

Background

Diffuse-type gastric cancer (DGC) exhibits rapid disease progression and poor patient prognosis. We have previously established an E-cadherin/p53 double conditional knockout (DCKO) mouse line as the first genetically engineered one, which morphologically and molecularly recapitulates human DGC. In this study, we explored low-molecular-weight drugs selectively eliminating mouse and human DGC cells.

Methods

We derived mouse gastric cancer (GC) cell lines from DGC of the DCKO mice demonstrating enhanced tumourigenic activity in immunodeficient mice and acquired tolerance to cytotoxic anti-cancer agents.

Results

We performed a synthetic lethal screening of 1535 annotated chemical compounds, and identified 27 candidates selectively killing the GC cell lines. The

SUBMITTER: Shimada S 

PROVIDER: S-EPMC5931092 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature