AIM: To investigate the roles and interactions of mut T homolog(MTH)-1 and hypoxia-inducible factor(HIF)-1α in human colorectal cancer(CRC).METHODS: The expression and distribution of HIF-1α and MTH-1 proteins were detected in human CRC tissues by immunohistochemistry and quantitative realtime polymerase chain reaction(q RT-PCR). SW480 and HT-29 cells were exposed to normoxia or hypoxia. Protein and m RNA levels of HIF-1α and MTH-1 were analyzed by western blotting and q RT-PCR, respectively. In order to determine the effect of HIF-1α on the expression of MTH-1 and the amount of 8-oxodeoxyguanosine triphosphate(d GTP) in SW480 and HT-29 cells, HIF-1α was silenced with small interfering RNA(si RNA). Growth studies were conducted on cells with HIF-1α inhibition using a xenograft tumor model. Finally, MTH-1 protein was detected by western blotting in vivo.RESULTS: High MTH-1 m RNA expression was detected in 64.2% of cases(54/84), and this was significantly correlated with tumor stage(P = 0.023) and size(P = 0.043). HIF-1α protein expression was correlated significantly with MTH-1 expression(R = 0.640; P < 0.01) in human CRC tissues. Hypoxic stress induced m RNA and protein expression of MTH-1 in SW480 and HT-29 cells. Inhibition of HIF-1α by si RNA decreased the expression of MTH-1 and led to the accumulation of 8-oxo-d GTP in SW480 and HT-29 cells. In the in vivo xenograft tumor model, expression of MTH-1 was decreased in the HIF-1α si RNA group, and the tumor volume was much smaller than that in the mock si RNA group.CONCLUSION: MTH-1 expression in CRC cells was upregulated via HIF-1α in response to hypoxic stress, emphasizing the crucial role of HIF-1α-induced MTH-1 in tumor growth. AIM: To investigate the roles and interactions of mut T homolog (MTH) -1 and hypoxia-inducible factor (HIF) -1α in human colorectal cancer (CRC). METHODS: The expression and distribution of HIF-1α and MTH-1 proteins were detected in human CRC tissues by immunohistochemistry and quantitative realtime polymerase chain reaction (q RT-PCR). SW480 and HT-29 cells were exposed to normoxia or hypoxia. Protein and m RNA levels of HIF-1α and MTH-1 were analyzed by Western blotting and q RT-PCR, respectively. In order to determine the effect of HIF-1α on the expression of MTH-1 and the amount of 8-oxodeoxyguanosine triphosphate (d GTP) in SW480 and HT- 29 cells, HIF- was silenced with small interfering RNA (si RNA). Growth studies were conducted on cells with HIF-1α inhibition using a Xenograft tumor model. Finally, MTH-1 protein was detected by western blotting in vivo .RESULTS: High MTH-1 m RNA expression was detected in 64.2% of cases (54/84), and this was highly correlated with tumor stag Hypoxic stress induced m RNA and protein expression of (p = 0.023) and size (p = 0.043). HIF-1α protein expression was significantly correlated with MTH-1 expression Inhibition of HIF-1α by si RNA decreased the expression of MTH-1 and led to the accumulation of 8-oxo-d GTP in SW480 and HT-29 cells. In the in vivo xenograft tumor model, expression of MTH-1 was decreased in the HIF-1α si RNA group, and the tumor volume was much smaller than that in the mock si RNA group. CONCLUSION: MTH-1 expression in CRC cells was upregulated via HIF- 1α in response to hypoxic stress, emphasizing the crucial role of HIF-1α-induced MTH-1 in tumor growth.