Results of a study on the effect of Notch signaling pathway inhibitors on ameloblastoma cell proliferation

Abstract

Background: Ameloblastoma (AB) is an odontogenic epithelial tumor. 80% of ameloblastomas occur in the jaw and often painlessly enlarge the jaw and cause facial deformity. Ameloblastoma is usually treated with a complete osteotomy, which is divided into three types: partial maxillary marginal resection, maxillary sinus resection, and total maxillary resection. These surgical procedures cause jaw deformity and facial trauma, so effective treatment methods with minimal trauma are still being sought in medicine. In order to develop new drugs for the treatment of ameloblastoma, it is necessary to study the molecular mechanisms that inhibit the proliferation of cancer cells. In recent years, it has been established that ameloblastoma is caused by abnormal activation of signaling pathways. Multiple signaling pathway regulators, target genes, and molecular interactions are involved in tumor cell proliferation and apoptosis. Previous studies have shown that blocking key signaling pathways is not only a therapeutic option in clinical practice, but also a useful tool in selecting tumor resection sites. Therefore, studying the molecular level of the Notch signaling pathway in the proliferation of ameloblastoma cells is of great importance for the treatment of the disease. Studies have shown that many factors of the Notch signaling pathway play important roles in promoting or inhibiting different tumors. The Notch signaling pathway promotes tumor cell proliferation by regulating CDK1, Cyclin D1, HES-1, and COX-2. Chinese researchers Li Wenchao and Baolidao’s research team have studied factors related to AB proliferation and invasion for the past decade, and have identified the roles of factors such as COX-2, Survivin, Akt, and PI3K in AB proliferation and invasion, and have successfully cultured primary ameloblastoma cells. However, the exact role of the Notch signaling pathway in AB cell proliferation has not been clearly studied. Aim: To study the effect of Notch signaling pathway inhibitors on ameloblastoma cell proliferation. Materials and Methods: The study was conducted at the Experimental Research Base of AfÏliated Hospital of Chifeng University, Inner Mongolia, China, using quantitative research methods and experimental research designs. The expression of Notch1, Cyclin D1, and CDK1 genes in AB cells was detected using real-time polymerase chain reaction. The effect of FLI-06 on the proliferation of AB cells after inhibition was studied by counting (CCK8) method. The ameloblastoma cell lines used in the study were obtained from the Experimental Research Base of AfÏliated Hospital of Chifeng University. The Notch signaling pathway inhibitor FLI-06 was purchased from Absin Bioscience Inc. (Absin® CAS: 313967-18-9), Shanghai. Results: In the study, real-time polymerase chain reaction analysis showed that the expression of Cyclin D1 in AB cells was 7.01 times higher than that in normal oral mucosa cells, the expression of CDK1 was 2.63 times higher, and the expression of Notch1 was 4.95 times higher. The cell proliferation of the control group was calculated as 100% by the AB cell proliferation inhibitor (CCK8) method, and compared with the experimental group, the cell proliferation of the group added with 5.0μM FLI-06 was 53.98%, 46.53% in the 10.0μM concentration group, and 22.33% in the 20.0μM concentration group. Conclusion: Notch1, Cyclin D1, and CDK1 expression in ameloblastoma were significantly different from that in normal oral mucosa cells. Inhibition of the Notch signaling pathway with FLI-06 reduced ameloblastoma cell proliferation.