Fluorouracil modulates the genome of HCT116 colorectal cancer cells as revealed by whole exome sequencing

Abstract

Abstract The Cancer mortality rate has globally increased by almost 40% over the past four decades. The mortality is expected to increase to 60% in the current decade, with an estimated death of 13 million cancer patients by 2030. Colorectal cancer (CRC) is the third most frequent type of cancer and the second leading cause of cancer-related deaths for both sexes, worldwide. Since CRC accounts for 10% of the most diagnosed types of cancer, there is an urgent need for developing treatment plans. In the present study, human colorectal carcinoma cells (HCT116) were challenged with and 5-fluorouracil (5 either alone or synergized by 5-Aza cytidine (5-Aza) at a final concentration of 5 µM. MTT, wound healing assay, and colony formation assays were performed to assess the cell viability, migration, and proliferation. Data indicated significant reductions in the viability of the 5-FU-treated cells synergized by 5-Aza compared to the monotherapy of both drugs. Whole exome sequencing (WES) was performed to assess the genetic changes after treatments. Results showed that 5-FU treatment significantly reduced the total number/type of SNPs of HCT116 cells, from 249,448 to 4,213 SNPs, with 3,521 novel SNPs. In conclusion, 5-Aza synergizes the effect of 5-FU by sensitizing HCT116; therefore, this combination could be optimal as a therapeutic option for CRC. Although these findings were promising, it needs further investigation at the pre-clinical and clinical levels.