Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

Objective： We aimed to perform a preliminary study of the association between induced pluripotent stem cell （iPS）-related genes and biological behavior of human colorectal cancer （CRC） cells, and the potential for developing anti-cancer drugs targeting these genes. Methods： We used real-time reverse transcriptase po- lymerase chain reaction （RT-PCR） to evaluate the transcript levels of iPS-related genes NANOG, OCT4, SOX2, C-MYC and KLF4 in CRC cell lines and cancer stem cells （CSCs）-enriched tumor spheres. NANOG was knockdowned in CRC cell line SW620 by lentiviral transduction. 3-（4,5-Dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） assays, plate colony formation, and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 cells. Also, mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil （5-FU） and survival rate was measured by MTT assay to evaluate drug sensitivity. Results： A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was observed. NANOG knockdown suppressed proliferation, colony formation, and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells. 5-FU treatment greatly inhibited the expression of the major sternness-associated genes NANOG, OCT4, and SOX2. Conclusions： These results collectively suggest an overlap between iPS-related genes and CSCs in CRC. Quenching a certain gene NANOG may truncate the aggressiveness of CRC cells.