Fig. 1: Effect of colon fibroblasts on colon cancer HCT116 cell DNA replication.

a, b DNA replication analysis of the HCT116 cells grown on fibroblasts suggested increased proliferation for cancer cells grown together with TAFs. c Naive colon fibroblasts and colon TAFs modify the circadian rhythm of HCT116 cell DNA replication. The circadian rhythm of DNA replication in HCT116 cells decreased significantly (p < 0.001) between 26 h and 32 h, followed by a significant increase (p < 0.001) between 32 and 38 h, and a significant decrease (p < 0.001) between 38 and 44 h. HCT116 cells co-cultured with TAFs showed a similar circadian pattern in DNA replication as the HCT116 cells from the single-cell-type culture: a significant decrease between 20 and 26 h (p < 0.01) and between 26 and 32 (p < 0.01) followed by a moderate insignificant increase between 26 and 32 h and a significant decrease between 38 and 44 h (p < 0.001). The HCT116 cells co-cultured with naive colon fibroblasts demonstrated a dampened DNA replication circadian rhythm. d HIFs modified the circadian growth rhythm of HCT116 cell DNA replication, showing diminished circadian amplitude in the cells co-cultured with HIFs. e Harmonic regression analysis curve of HCT116 cells, HCT116 cells co-cultured with naive fibroblasts, and HCT116 cells co-cultured with TAFs. f Harmonic regression analysis parameters of HCT116 cells and HCT116 cells co-cultured with naive fibroblasts and HCT116 cells co-cultured with TAFs. The acrophase shift was calculated relative to the HCT116 cell control sample. g Harmonic regression analysis curve of HCT116 cells and HCT116 cells co-cultured with HIFs. h Harmonic regression analysis parameters of HCT116 cells and HCT116 cells co-cultured with HIFs. The acrophase shift was calculated relative to the HCT116 cell control sample. The p-values are *p < 0.05, **p < 0.01, and ***p < 0.001.