Circadian Clock Gene BMAL1 and Hypoxia Inducible Factor HIF-1α Study on the Effect on Proliferation, Migration and Radiosensitivity of Nasopharyngeal Carcinoma Cells

Abstract

<h3>Purpose/Objective(s)</h3> To investigate the relationship between biological clock gene BMAL1 and hypoxia inducible factor-1α at the protein level and their effects on the proliferation, migration and radiosensitivity of nasopharyngeal carcinoma cells. <h3>Materials/Methods</h3> The cell line was constructed by infecting lentivirus. Western blot analysis was used to verify the infection efficiency and the relationship of BMAL1 gene and HIF-1α in nasopharyngeal carcinoma cells. A cell counting kit cell proliferation test was used to detect the proliferation ability of nasopharyngeal carcinoma cells, scratch test was used to detect the migration ability of nasopharyngeal carcinoma cells, flow cytometry was used to detect apoptosis, and clone formation test was used to detect the effects of BMAL1 and HIF-1α on the radiosensitivity of hone1 nasopharyngeal carcinoma after different doses (0, 2, 4, 6gy) of X-ray irradiation. <h3>Results</h3> Compared with the control group, overexpression of BMAL1 can inhibit the protein expression of HIF-1α in nasopharyngeal carcinoma cells, silencing BMAL1 can promote the protein expression of HIF-1α in nasopharyngeal carcinoma cells. The mechanism of BMAL1 may be related to HIF-1α. The cell counting kit cell proliferation test and scratch test showed that BMAL1 overexpressed or HIF-1α gene silencing could reduce the proliferation and migration of nasopharyngeal carcinoma cells (P <0.05). The apoptosis rate after radiotherapy in the interference group was higher than that in the control group (P<0.05). The apoptosis rate of BMAL1 overexpression group or HIF-1α Interference group after radiotherapy was higher than that of control group (P< 0.05). Clone formation test showed that the clone formation rate and survival score of BMAL1 overexpression group or HIF-1α Interference group were lower than those of negative control group. The radiosensitization ratio of BMAL1 overexpression group was 1.381 and the radiosensitization ratio of HIF-1α interference group was 1.063, the difference was statistically significant. <h3>Conclusion</h3> BMAL1 may affect the protein expression of HIF-1α in protein level. High expression of BMAL1 or interference with HIF-1α can inhibit the proliferation and migration of nasopharyngeal carcinoma cells, increase apoptosis after radiotherapy and improve radiosensitivity.