Effect of phospholipase D1 inhibitory cell permeable chimera peptide on the growth and metastasis of AGS gastric cancer cells Dong-Ju Kim

Abstract

Effect of phospholipase D1 inhibitory cell permeable chimera peptide on the growth and metastasis of AGS gastric cancer cells Dong-Ju Kim Dept. of Biomedical Science The Graduate School of Biomedical Science and Engineering Phospholipase D1 (PLD1) is an enzyme that hydrolyzes phosphatidyl choline into choline and phosphatidic acid (PA). Several studies reported that PLD1 activity and expression are increased in cancer, and engaged in multiple stages of cancer progression. To examine the effect of PLD1 inhibitory peptide on the growth of gastric cancer cells (AGS), we constructed TAT-TVTSP, a PLD1-inhibitory peptide (TVTSP) fused with a cell-penetrating peptide (TAT) delivery system. In AGS cells, TAT-TVTSP inhibited PLD1 activity. We found that TAT-TVTSP decreased mTOR signaling activity including its downstream S6K1, AKT S473, GSK3b, and FOXO1. We also confirmed that TAT-TVTSP does not induce cell death, but induce cell cycle arrest. TAT-TVTSP inhibited the ability of a single cell to grow through colony formation assay. Moreover, we showed that TAT-TVTSP disrupted cell migration and invasion in transwell assay and wound-healing assay. Additionally, in xenograft model, TAT-TVTSP significantly suppressed tumor growth without toxicity. Taken together, these results indicated that TAT-TVTSP might be used as a novel candidate to treat cancers.