Inhibition of PCSK9 protects against radiation-induced damage of prostate cancer cells

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein expressed primarily in the liver, formerly known to maintain plasma lipid homeostasis by regulating lowdensity lipoprotein receptor levels, and its exact role in the radioresistance of prostate cancer (PCa) remains unclear. We aim to investigate the function of PCSK9 in the radioresistance of PCa cells. Methods: PCSK9 small interfering RNA (siRNA) was introduced into the PCa cells by transient transfection. Then, cells were exposed to ionizing radiation (IR) at indicated dose rates. Cell damage was detected using cell counting kit-8 (CCK-8) and Hoechest 33342/propidium iodide (PI) staining. Rhodamine-123 (Rho-123) dye was used to assay mitochondrial membrane potential alteration. Western blot was used to detect the apoptosis-related protein expression. Results: PCSK9 siRNA treatment significantly protected PCa cells from IR-induced cell damage, including enhancing cell viability, reducing apoptosis, and inhibiting MMPs. Moreover, PCSK9 siRNA repressed the increase of cytochrome C (cyto C), caspase-3, and B-cell leukemia/ lymphoma 2 (Bcl-2)-associated X (Bax) expressions induced by IR and promoted Bcl-2 expression, which might partially interpret the radioprotective role of PCSK9 siRNA in PCa cells. Conclusion: PCSK9 might impact on radiosensitivity through mitochondrial pathways and serve as a novel therapeutic target for PCa patients.