Anti-Cancer Effects of Combination Treatment of Butyrate and 5-Fluorouracil in Gastric cancer cells

다국어 초록 (Multilingual Abstract)

Anti-Cancer Effects of Combination Treatment of Butyrate and 5-Fluorouracil in Gastric cancer cells by Su Rim Kim Master of Medicine Graduate School of Kyung Hee University Advised by Dr. In Sug Kang This research aims to elucidate the effect and mechanism by which Butyrate (BA), a type of short-chain fatty acid produced by intestinal microbiota fermentation, enhances the anticancer efficacy of the first-line anticancer agent, 5-Fluorouracil (5-FU), in gastric cancer cells. BA increased cell apoptosis induced by 5-FU in AGS and MKN-45 cells, as evidenced by elevated levels of cleaved-Caspase-3, cleaved-PARP, and BAX expression, along with a decrease in Bcl- 2 expression. BA also augmented the G0/G1 cell cycle arrest effect induced by 5-FU. Additionally, the involvement of autophagy in the synergistic cytotoxicity of combination treatment was confirmed using autophagy inhibitors, as indicated by increased LC3- II conversion and p62 degradation. The observed cytotoxic effects were found to be associated with the modulation of AMPK, ERK, and PI3-kinase pathways, demonstrated through the use of protein kinase inhibitors. Furthermore, the study revealed the involvement of BA’s role as a histone deacetylase (HDAC) inhibitor in the combination treatment. Finally, BA was shown to enhance the inhibitory effects of 5-FU on cancer cell migration and invasion, with increased reactive oxygen species (ROS) accumulation playing a role in these metastatic processes. In conclusion, this study demonstrates that BA enhances the cytotoxic effects induced by 5-FU in gastric cancer cells and provides insights into the underlying mechanism involved.

목차 (Table of Contents)

• Abstract i
• 1. Introduction · 1
• 2. Materials and Methods · 3
• 3. Results · 7
• 4. Discussion · 28
• 5. Summary 30
• 6. References · 31
• 7. Korean Abstract 33
• Figure Contents
• Figure 1. 8
• Figure 2. 10
• Figure 3. 12
• Figure 4. 15
• Figure 5. 17
• Figure 6. 19
• Figure 7. 22
• Figure 8. 24
• Figure 9. 27