부산대학교 도서관

Background Natural chemical SAM (S-adenosylmethionine) is present in all living cells and plays an important role in biological transmethylation. Recent studies have shown that SAM possesses many pharmacological activities including anti-cancer effects. However, the complex formation of SAM with gemcitabine on pancreatic carcinoma cells, as well as the specific mechanism, remains unknown. Objectives Pancreatic cancer cells (PANC-1 and BxPC-3) were treated with SAM and/or gemcitabine and subjected to MTT, combination index, cell apoptosis, cell migration, western blot, and xenograft tumorigenicity assays in this research. Results The findings revealed that SAM might synergistically improve gemcitabine’s capacity to prevent the development and proliferation of pancreatic cancer cells. By decreasing the EGFR/AKT pathways, SAM in combination with gemcitabine might promote cell death and impede cell migration. Furthermore, pretreatment with IGF-1 (a particular AKT activator) drastically reduced SAM’s pro-apoptotic activity in pancreatic cancer cells, demonstrating the importance of AKT in this mechanism. Furthermore, following treatment with SAM with gemcitabine, tumor volume and weight were considerably decreased in the PANC-1 xenograft mouse model, and immunohistochemical analysis confi rmed the down-regulation of p-EGFR and p-AKT in tumor tissues. Conclusion By suppressing the EGFR/AKT pathways, SAM could synergistically boost the inhibitory impact of gemcitabine on pancreatic cancer cells and might be a promising therapeutic drug for the management of pancreatic cancer.