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

Authors Gan S, Ye J, Wang L, Qu F, Chu C, Tian Y, Yang W, Cui X

Received 4 December 2016

Accepted for publication 1 March 2017

Published 12 April 2017 Volume 2017:10 Pages 2139—2146

DOI https://doi.org/10.2147/OTT.S129413

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai

Si-Shun Gan,* Jian-Qing Ye,* Lei Wang, Fa-Jun Qu, Chuan-Min Chu, Yi-Jun Tian, Wei Yang, Xin-Gang Cui

Department of Urinary Surgery of Third Affiliated Hospital, Second Military Medical University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

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 low-density 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.

Keywords: PCSK9, prostate cancer, radioresistance, mitochondrial pathway

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