Abstract
BackgroundOur study aims to evaluate the anti-growth effects of recombinant immunotoxin (IT) anti-c-Met/PE38KDEL on gastric cancer cells, and its mechnisms.MethodsGastric cancer cells were treated with increasing doses of IT and c-Met protein was quantified by Western blotting. Cell proliferation was determined by Cell Counting Kit-8 assay (CCK). [3H]-leucine incorporation assay was used to evaluate IT inhibition of protein synthesis. Cell apoptosis was quantified by flow cytometry. Caspase activities were measured using colorimetric protease assays.ResultsCell growth and protein synthesis of the gastric cancer cell lines were suppressed by IT in a dose- and time-dependent manner. IT also induced apoptosis in a dose-dependent manner. The apoptosis rates of gastric cancer cell lines MKN-45 and SGC7901 were 19.19% and 27.37%, respectively when treated with 50 ng/ml of IT. There were significant increase ofcaspase-3 activity at 24 hr of IT treatment (100 ng/ml) (P < 0.01) in these gastric cancer cell lines.ConclusionsIT anti-c-Met/PE38KDEL has anti-growth effects on the gastric cancer cell lines in vitro, and it provides an experimental basis for c-Met-targeted therapy towards in vivo testing.
Highlights
Gastric carcinoma (GC) is one of the most common and lethal malignant cancers [1]
We investigated the effects of IT anti-c-Met/PE38KDEL on proliferation and apoptosis of two different c-Met-positive malignant gastric cell lines, MKN-45 and SGC7901 [11,12], and a normal gastric mucosa cell GES-1 [13]
MKN-45 and SGC7901 had a 0.94 and 1.27 fold increase in the expression of c-Met over the control, but only 0.34 fold increased in GES-1
Summary
Gastric carcinoma (GC) is one of the most common and lethal malignant cancers [1]. GC has been shown to harbor multiple somatic mutations as well as over-expressions of oncoproteins. Identification of these GC-associated biomarkers may entail possible discovery of new therapeutic targets [3]. Among various GC-associated biomarkers, c-MET gene is frequently found gnomically-amplified and overexpressed in GC cell lines [4]. The proto-oncogene cMET, a receptor of hepatocyte growth factor (HGF, known as scatter factor), encodes a 190 kDa heterodimeric transmembrane tyrosine kinase. HGF binding to c-Met triggers tyrosine kinase domain auto-. Our study aims to evaluate the anti-growth effects of recombinant immunotoxin (IT) anti-c-Met/ PE38KDEL on gastric cancer cells, and its mechnisms
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