Targeting UNC-51-like kinase 1 can inhibit esophageal cancer cell proliferation and regulate autophagy

Abstract

Abstract The purpose of this study was to investigate the expression of UNC-51-like kinase 1 (ULK1) in esophageal cancer(ESCA) and its prognostic value, its effect on esophageal cancer cell growth and proliferation, and the synergistic effect of its inhibitor and cisplatin on esophageal cancer cells. Methods: 1. The expression and prognosis of ULK1 in pancancer and ESCA were analyzed with the TCGA database. 2. The effect of ULK1 knockdown on the proliferation of esophageal cancer ECA109 cells was observed in the plate colony formation assay. 3. CCK-8 assay, flow cytometry and Western blotting were used to explore the synergistic effect of cisplatin and a ULK1 inhibitor on the apoptosis of esophageal cancer cells. 4. Bioinformatics and Western blotting were used to analyze the possible mechanism by which ULK1 regulates ESCA. Results: 1. ULK1 was highly expressed in esophageal squamous cell carcinoma (ESCC) and was negatively correlated with the prognosis of patients. 2. Knockdown of ULK1 reduced the proliferation ability of esophageal cancer cells; 3. The combination of a ULK1 inhibitor and cisplatin enhanced the toxicity to ESCC cells and induced apoptosis. 4. ULK1 may be related to autophagy in ECA cells, and the combination of a ULK1 inhibitor and cisplatin can enhance the toxicity of cisplatin by inhibiting autophagy. Conclusion: Knockdown of ULK1 or the use of small molecule inhibitors can inhibit the proliferation of esophageal cancer cells, induce apoptosis, and enhance the toxicity of chemotherapeutic drugs on esophageal cancer cells, which may be related to the regulation of autophagy.