Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

He,Zhenhua; Yuan,Jingmin; Qi,Ping; Zhang,Lixiu; Wang,Zhiping

doi:10.3892/mmr.2015.3334

Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

Authors:
- Zhenhua He
- Jingmin Yuan
- Ping Qi
- Lixiu Zhang
- Zhiping Wang
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Affiliations: School of Life Sciences, Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Pain, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China, Institute of Urology and Key Laboratory of Urological Diseases in Gansu, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China
Published online on: February 11, 2015 https://doi.org/10.3892/mmr.2015.3334
Pages: 4403-4408

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Abstract

Athough it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy‑associated gene expression profile in the PC3 prostate carcinoma cell line. The atorvastatin‑induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)‑II, using immunoblotting and counting of green fluorescent protein (GFP)‑LC3-transfected autophagic cells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Atorvastatin treatment of PC3 cells for 24 h increased the expression of green fluorescent protein‑LC3‑II by >25%, and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression.

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