Abstract 2115: FOS contributes to 5-FU resistance and reversal effects of natural flavonoid GL-V9 in colon cancer

Abstract 5-FU is widely used in the treatment of colon cancers. Although 5-FU can improve response rates and survival, response rates for 5-FU-based chemotherapy as a first-line treatment for advanced colorectal cancer are only 10-15%. Meanwhile, cancer drug resistance often occurs, which is an important reason for poor treatment effect of 5-FU. Therefore, it is significant to uncover the mechanisms underlying 5-FU resistance and develop effective but nontoxic agent candidates for reversing cancer drug resistance. Here, we found that proto-oncogene FOS was activated in 5-FU-resistant colon cancer cells compared to parental cells. Additionally, FOS overexpression using lentivirus plasmid obviously triggered 5-FU resistance in colon cancer cells. Moreover, by analyzing two GEO datasets, we also found that FOS expression was associated with poor overall survival of colon cancer. Taken together, FOS confers 5-FU resistance to colon cancer and it is potential to be exploited as a therapeutical target. Lastly, we studied the reversal effects of natural flavonoid GL-V9 on the FOS activation and 5-FU resistance in order to develop candidates for FOS inhibitor which would be helpful for 5-FU-resistant colon cancer. Consequently, nontoxic doses of GL-V9 could significantly suppress activation of FOS and sensitize colon cancer cells to 5-FU. Therefore, the flavonoid is potential to be exploited as a synergetic agent for 5-FU-resistant colon cancer. Note: This abstract was not presented at the meeting. Citation Format: Li Zhao, Li Zhaohe, Ding Youxiang. FOS contributes to 5-FU resistance and reversal effects of natural flavonoid GL-V9 in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2115.