E3泛素连接酶CDC20对前列腺癌细胞放射敏感性的影响及机制研究

objective: To explore the expression of CDC20 in human prostate cancer and its impact on patient prognosis; To investigate the effect of knocking down CDC20 expression on the radiosensitivity of prostate cancer cells and its mechanism. Methods: CDC20 expression in human prostate cancer tissues and its influence on the prognosis of patients were analyzed with information from TCGA and GTEx databases. The expression of CDC20 mRNA and protein in the prostate cancer cells and normal prostate epithelial cells was detected by RT-PCR and Western Blotrespectively. Silencing CDC20 prostate cancer cells were established by RNA interference technology. Clone formation assay and tumor xenograft animal models were performed to assess the effect of knocking down CDC20 on the radiosensitivity of prostate cancer cells in vitro and in vivo. Western blotting was performed to detect the protein expression of CDC20 and Bim. Apoptosis detection of prostate cancer cells was conducted through flow cytometry. Cell viability was detected using CCK8 assay.Results: Bioinformatics analysis showed that CDC20 was highly expressed in prostate cancer tissues, andpatients with higher CDC20 expression had significantly reduced overall survival and disease-free survival. Prostate cancer cells express higher levels of CDC20 than normal prostate epithelial cells. The expression of CDC20 was significantly up-regulated 24h after different doses of X-ray irradiation. Western Blot confirmed the successful construction of CDC20 knockdown prostate cancer cells. Colony formation assay confirmed that knockdown of CDC20 expression improved the radiosensitivity of prostate cancer cells. CDC20 knockdown promoted ionizing radiation-induced apoptosis and enhanced the inhibitory effect of ionizing radiation on cell viability. Knockdown of CDC20 expression enhanced the growth inhibitory effect of ionizing radiation on PC3 xenograft tumors. CDC20 negatively regulated the abundance of Bim protein inprostate cancer cells. Knockdown CDC20increased ionizing radiation-induced apoptosis, while knockdown Bimdecreased apoptosis, the inhibitory effect of Bim knockdown on apoptosis in prostate cancer cells was reversed by CDC20 knockdown. Knockdown of CDC20 enhanced the inhibitory effect of ionizing radiation on cell viability, while Bim knockdown weakened the inhibitory effect on cell viability, the effect of Bim knockdown on cell viability in prostate cancer was reversed by the knockdown of CDC20. Conclusion: CDC20 is highly expressed in human prostate cancer, and the CDC20 expression level is negatively correlated with the prognosis of prostate cancer patients. Ionizing radiation increases CDC20 expression in prostate cancer cells. CDC20 knockdown induces cell apoptosis through the Bim pathway and enhances the radiosensitivity of prostate cancer cells.