We Hypothesize That BMAL1 Has a Positive Regulatory Effect on the Radiosensitivity of Nasopharyngeal Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> BMAL1 is a core biological clock gene, which is expressed rhythmically in a variety of tumor cells, and is related to cancer cell proliferation and chemotherapy sensitivity. Radiotherapy is the main treatment for nasopharyngeal carcinoma (NPC). However, the role of baml1 in radiotherapy for nasopharyngeal carcinoma is unclear. <h3>Materials/Methods</h3> We used 5 types of nasopharyngeal carcinoma cells (CNE1, CNE2, HONE1, C666-1, 5-8F) and normal nasopharyngeal epithelial cells NP69 as the research objects, and detected the transcription level changes of BMAL1 mRNA within 24 hours by RT-PCR. Furthermore, after overexpression and knockdown of BMAL1 in nasopharyngeal carcinoma CNE1 cells and transplanted tumors in nude mice, the effects of BMAL1 on the proliferation of CNE1 cells and subcutaneous transplanted tumors and the changes after radiotherapy were observed. Finally, RT-PCR and Western Blot were used to detect BMAL1, P53, P21 gene and protein expression in tumor tissues. <h3>Results</h3> The results suggest that the expression level of the circadian clock gene BMAL1 in NPC cell lines and NP69 cells fluctuates with time. Overexpression of BMAL1 can inhibit the proliferation of NPC cells, while knockdown promotes the proliferation of NPC cells. In the xenograft model, we observed that up-regulation of BMAL1 inhibited tumor growth and enhanced the sensitivity of NPC cells to radiotherapy, accompanied by increased expression of P53 and P21. Down-regulating BMAL1 promotes tumor growth, reduces the sensitivity of radiotherapy, and decreases the expression of P53 and P21. <h3>Conclusion</h3> BMAL1 showed rhythmic expression in NPC cells and NP69. BMAL1 plays a tumor suppressor effect in NPC, and can increase the sensitivity of NPC to radiotherapy, which may be related to the up-regulation of P53 and P21 protein expression. It is speculated that BMAL1 may become a new prognostic biomarker and new therapeutic target for NPC.