Abstract C35: Low-dose imatinib mesylate suppressed PDGF-BB mediated motility and invasion of gastric cancer cells

Purpose Imatinib mesylate is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases and is used in treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), and other cancers. Although imatinib has not yet been used in gastric cancer, we verified that high-dose imatinib leads gastric cancer cell lines to apoptosis via down regulation of Akt phosphorylation in previous study. This study was undertaken to evaluate the in vitro effect of low-dose imatinib in inhibition of invasion and migration of gastric cancer cells and to define molecular mechanism underlying these effects. Methods This study was to determine the expression of PDGFR molecules in gastric cancer cells (four human gastric cancer cell lines; AGS, MKN28, MKN45, and SNU638) by semi-quantitative polimerase chain reaction (PCR). The effects of low-dose imatinib (≤20uM.ml) on cell viability were examined using MTT assay. The effects of imatinib and PDGF-BB on cell motility and cell invasion were studied using wound healing assay and matrigel invasion assay respectively. Results The results showed expression of PDGFR in all four gastric cancer cells. We measured the sensitivity of gastric cancer cell line (AGS, MKN28, MKN45, SNU638) to imatinib using MTT assay. Cell viability of low-dose imatinib treated cell was not decreased. However, cell migration and invasion was decreased with low-dose imatinib. When PDGF-BB was added, cell motility and invasion were activated. However, when both PDGF-BB and imatinib were added, that activation was not shown. Conclusion In conclusion, low-dose imatinib mesylate inhibits PDGF-BB mediated cell migration and invasion not decreasing cell viability. The results suggest that imatinib mesylate may be useful in the treatment of gastric cancer. Citation Format: Hong Jun Kim, Suk Young Lee, Sang Cheul Oh, Jun Suk Kim, Jung Lim Kim, Bo Ram Kim, Yoo Jin Na. Low-dose imatinib mesylate suppressed PDGF-BB mediated motility and invasion of gastric cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C35.