Abstract

The incidence of colorectal cancer (CRC) has remained high in recent years, and 5‑fluorouracil (5‑FU) is a vital chemotherapeutic agent for its treatment. Our previous study reported that N‑myc downstream‑regulated gene 4 (NDRG4) plays a tumor‑suppressive role in CRC, but the mechanisms associated with NDRG4 and 5‑FU chemosensitivity remain unclear. The results of the present study demonstrate that NDRG4 sensitized CRC cells to 5‑FU by upregulating DNA damage inducible transcript 3 (DDIT3). NDRG4 inhibited the proliferation of CRC cells and the activation of PI3K/AKT and ERK signaling. Furthermore, NDRG4 promoted CRC cell apoptosis induced by 5‑FU. Mechanistic analyses revealed that NDRG4 upregulated DDIT3 expression, and that the proapoptotic effect of NDRG4 under 5‑FU treatment conditions was dependent on DDIT3. These findings support the biological value of the association between NDRG4, DDIT3 and 5‑FU chemosensitivity in CRC, and may advance the clinical treatment of CRC in the future.