e15553 Background: Gastric cancer, a highly aggressive malignancy, frequently recurs despite curative surgery and metastasizes to lymph node and distant sites. Epithelial-mesenchymal transition (EMT) is the main phenomenon of cancer progression, including invasion and metastasis. It is regulated by crosstalks between diverse intracellular signaling pathways such as Wnt/β-catenin and phosphatidylinositol-3-kinase(PI3K)/Akt/ mammalian target of rapamycin (mTOR) pathways. Here, this study elucidated the effects of co-inhibition of Wnt/β-catenin and PI3K/Akt/mTOR pathways on gastric cancer. Methods: It is known that Wnt/β-catenin signaling pathways are constitutively activated in two of gastric cancer cell lines, AGS and MKN-28. ICG-001 (β-catenin transcription inhibitor) and rapamycin (mTOR inhibitor) were used for dual blockade, and then the combinatory effects were examined. Results: As a result, both cell lines were significantly affected by the β-catenin transcription inhibitor, ICG-001, and addition of the mTOR inhibitor, rapamycin induced marginal inhibitory effects on cancer cell proliferation and target gene expression. In addition, invasive activity was 62.3 ± 15.7% and 53 ± 14.4% inhibited by single treatment, but it was 79 ± 13.3% inhibited by co-treatment. Moreover, migratory activity was 33 ± 13%, 42 ± 9% inhibited by single treatment, but it was 82 ± 4% by co-treatment. Interestingly, Snail, one of the important regulatory protein during EMT process, was significantly decreased by co-treatment. Conclusions: Taken together, these results suggest that co-inhibition of Wnt/β-catenin and PI3K/Akt/mTOR pathways could effectively enhance antitumor effects on gastric cancer via the inhibition of invasion and migration as well as decrease of Snail expression.
Antitumor effects of seleno-short-chain chitosan (SSCC) against human gastric cancer BGC-823 cells