Knockdown of FBP1 enhances radiosensitivity in prostate cancer cells by activating autophagy

For patients with clinically early-stage localized prostate cancer, radiotherapy is another treatment that can achieve radical treatment in addition to radical prostatectomy.Despite this, there are still a large number of patients with prostate cancer who have a biochemical recurrence after undergoing radiotherapy, or even clinical recurrence, leading to treatment failure.Although the expression of the fructose-1,6-bisphosphatase 1 (FBP1) gene has been found to be absent in various tumors and is associated with a poor prognosis in tumor patients.However, the expression and role of FBP1 in prostate cancer are not clear.The purpose of this study was to investigate the role and mechanism of FBP1 in the radiotherapy resistance of prostate cancer.By analyzing the microarray data of prostate cancer radiotherapy resistant cells and parental cells (GSE53902), we found that FBP1 expression in DU145 radiotherapy resistant cells was significantly higher than in the DU145 parental cells.In addition, we searched for the expression of FBP1 in 492 prostate cancer samples from TCGA and found that its expression in prostate cancer was significantly higher than that in normal tissues.Knockdown of FBP1 expression significantly inhibited the proliferation of prostate cancer cells, promoted DNA damage-mediated apoptosis, and enhanced the sensitivity of prostate cancer cells to radiotherapy.Further mechanism analysis revealed that FBP1 knockdown could activate autophagy mediated by the AMPK-mTOR signaling pathway, while inhibition of the AMPK-mTOR signaling pathway could reverse FBP1 knockdown-mediated autophagy and apoptosis, as well as radiosensitization.In conclusion, this study clarified that FBP1 is an oncogene in prostate cancer, and the main mechanism for knockdown of FBP1 to increase radiosensitivity is to enhance autophagy mediated by the AMPK-mTOR signaling pathway.Therefore, FBP1 may be a potential target for enhancing prostate cancer radiotherapy.