Purpose: This study explored the effects of phosphofructokinase-1 (PFK1) on the radiosensitivity of colorectal cancer (CRC) in vivo and in vitro and the underlying mechanisms.
Methods: Tissue samples from 48 patients with rectal cancer who had received neoadjuvant radiotherapy followed by surgery were analyzed. The expression of PFK1 in tissue samples was semi-quantitated by immunohistochemistry, and its relationship with clinicopathological features was analyzed. The effects of PFK1 knockdown on the survival, apoptosis, migration, and radiosensitivity of CRC cells were evaluated. Glycolysis-related indicators were used to examine glycolytic activity. The effects of PFK1 on the radiosensitivity of CRC in vivo were assessed by measuring tumor formation in nude mice.
Results: PFK1 was overexpressed in rectal cancer and was higher in radiation-resistant tumors than in radiation-sensitive tumors. SiRNA-induced PFK1 silencing increased apoptosis and inhibited migration and proliferation of CRC cells. Knockdown of PFK1 made the CRC cells sensitive to ionizing radiation in vivo. Oligomycin partially restored the expression of PFK1, enhanced glycolysis, and reversed the enhanced radiosensitivity of CRC cells induced by siRNA-PFK1. Downregulation of PFK1 combined with irradiation inhibited growth of nude mice xenografts, which was related to an increase in apoptosis.
Conclusions: Our study indicates that high expression of PFK1 is negatively correlated with radiosensitivity in CRC and likely accelerates the proliferation and migration of CRC cells. Downregulation of PFK1 may enhance the radiosensitivity of CRC cells in vivo and in vitro by inhibiting glycolysis.
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