The effect of alloferon on chemosensitivity of pancreatic cancer through the regulation of SLC6A14 expression

Abstract

Abstract Pancreatic cancer is one of the most malignant solid tumors with a high mortality rate. Although there have been many trials for effective therapies using chemotherapeutic drugs, such as gemcitabine, pancreatic cancer still shows significantly higher mortality than other types of cancer. Therefore, it is needed to examine the effective therapeutic ways to improve conventional therapy for pancreatic cancer. It has been previously reported that cancer cells possess a high rate of glutamine uptake needed for their rapid proliferation. In addition, it has recently been reported that amino acid transporter SLC6A14 is up-regulated in some cancers in close relation to glutamine metabolism. Alloferon is a peptide isolated from the insect immune system and shows anti-viral and anti-inflammatory effects based on its immune modulating function. In addition, its anti-tumor effect was recently discovered, but the related mechanisms are largely unknown. For this reason, I investigated the effect of alloferon on pancreatic cancer cell lines Panc-1 and AsPC-1. When Panc-1 and AsPC-1 were exposed to alloferon for 3 weeks, I found down-regulation of SLC6A14 expression and decreased glutamine uptake. Given that SLC6A14 is involved in tumor progression and survival by promoting glutamine uptake into cancer cells, alloferon could be an effective way with conventional chemotherapeutic drug, gemcitabine. Therefore, alloferon could be a useful adjuvant for an effective therapeutic way with conventional chemotherapeutic drug, gemcitabine. This study was funded by the NRF of Korea (No.:2017R1A2B2010948, 2017R1A6A3A11032576, 2020R1C1C1009334)