Cell Killing and Radiosensitizing Effects of Atorvastatin in PC3 Prostate Cancer Cells
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- HE Zhenhua
- University of Houston at Clear Lake
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- MANGALA Lingegowda S.
- University of Houston at Clear Lake NASA Johnson Space Center
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- THERIOT Corey A.
- NASA Johnson Space Center
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- ROHDE Larry H.
- University of Houston at Clear Lake
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- WU Honglu
- NASA Johnson Space Center
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- ZHANG Ye
- NASA Johnson Space Center Wyle Integrated Science and Engineering Group
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Recent studies have indicated that autophagy may be one of the important pathways induced by ionizing radiation. Atorvastatin (statin), an inhibitor of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, may exhibit anticancer effects as an autophagy inducer. In our study, the cell killing and radiosensitizing effects of statin were analyzed in PC3 cell line. Activation of the autophagy pathway was analyzed using the GFP-LC3 assay and western blot to determine LC3-II expression. The radiosensitivity of PC3 cells was determined using the clonal survival assay, TUNEL assay, and the Annexin V apoptosis assay. The expression profiles of autophagy related genes were analyzed using a pathway specific real-time polymerase chain reaction (PCR) array. Autophagic response was induced in PC3 cells after exposure to statin and/or gamma rays. Inhibition of the autophagic process using small interfering RNAs (siRNA) targeting Atg7 and/or Atg12 significantly reduced radiosensitivity of PC3 cells. Statin also exhibited a significant apoptosis-inducing effect in PC3 cells, which can be partially suppressed by Atg7 siRNA. Cells treated with statin and gamma irradiation showed significantly reduced colony forming efficiency and increased number of Annexin V positive early apoptotic cells. Analysis of autophagy and its regulatory gene profile showed that the expressions of 22 genes out of 86 genes assessed were significantly altered in the cells exposed to combined treatment or statin alone. The data indicate that activation of the autophagy pathway may be responsible for apoptosis inducing effect of statin. Furthermore, combined treatment with radiation and autophagic inducer, such as statin, may be synergistic in inducing cell death of PC3 cells.
収録刊行物
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- Journal of Radiation Research
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Journal of Radiation Research 53 (2), 225-233, 2012
Journal of Radiation Research 編集委員会
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詳細情報 詳細情報について
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- CRID
- 1390282680191780224
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- NII論文ID
- 130001876832
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- NII書誌ID
- AA00705792
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- COI
- 1:STN:280:DC%2BC38rlsl2htA%3D%3D
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- ISSN
- 13499157
- 04493060
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- NDL書誌ID
- 023572143
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- PubMed
- 22510595
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可