Abstract
Abstract Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases that is used in the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), and other cancers. But, imatinib mesylate has not yet been reported about anti-cancer effect in gastric cancer. This study was undertaken to evaluate the in vitro effect of imatinib mesylate in gastric cancer cells and to define molecular mechanism underlying these effects. This study was to determine the expression of PDGFR molecules in gastric cancer cells (AGS, MKN28, MKN45, SNU638) by semi-quantitative polimerase chain reaction (PCR). The effects of imatinib mesylate on gastric cancer cells were examined in four human gastric cancer cell lines. 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 mesylate using MTT assay. Cell viability of cell treated with imatinib mesylate was decreased in high dose. But cell viability was not change in high dose. Next, the results showed expression of PDGFR and suppression of its phosphorylation by imatinib mesylate in all four gastric cancer cells. Cell cycle analysis for sub-G1 and G2/M fraction also detected the increased cell death in the cells treated with imatinib mesylates. Results by Western blotting indicated that imatinib mesylates promotes apoptosis of gastric cancer cells by both activating caspase-3 and -9 and inducing PARP cleavage. And expression of p-AKT level was decreased. Cell migration and invasion that imatinib treated cells is decreased in low dose. Cell viability assay revealed that the combination of imatinib mesylate and chemo-reagent synergistically inhibited cell growth compared to cells treated with any of the agent alone. In conclusion, inhibition the PDGFR by imatinib mesylates lead to apoptosis of gastric cancer cell lines. And Imatinib suppressed motility and invasion of gastric cancer cells. The results suggest that imatinib mesylate may be useful in the treatment of gastric cancer. Note: This abstract was not presented at the meeting. Citation Format: Jung Lim Kim, Bo Ram Kim, Yoo Jin Na, Seong Hye Park, Yoon A Jeong, Sang Cheul Oh. Effect of Imatinib mesylate in gastric cancer cell progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3805. doi:10.1158/1538-7445.AM2015-3805
Published Version
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