Enhancement of Radiosensitivity by Roscovitine Pretreatment in Human Non-small Cell Lung Cancer A549 Cells
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概要
- 論文の詳細を見る
Roscovitine has been reported to have anti-proliferative properties and is in process of undergoing clinical trials. In addition to its intrinsic anticancer properties, it has recently been suggested that roscovitine may also enhance the activity of traditional chemo- and radio-therapies in certain cancer cell lines. The purpose of this study was to define the activity of roscovitine in increasing radiosensitivity of human non-small cell lung cancer (NSCLC) cell line A549 cells in vitro. A549 cells were exposed to ionizing radiation (IR) of γ-ray with or without roscovitine pretreatment. Clonogenic assay was performed and cell cycle and apoptosis were analyzed by flow cytometry. Expression of PARP, Ku70 and Ku80 proteins was detected by Western blot. The active form of caspase-3 positive cells were measured by flow cytometry. Our results showed that roscovitine caused dose-dependent apoptosis in A549 cells. Pretreatment with minimally toxic concentration of roscovitine significantly radiosensitized A549 cells by inhibiting colony formation. We then examined potential mechanisms that may contribute to the enhanced radiation response induced by roscovitine. Our results showed that the combination treatment significantly induced apoptosis in A549 cells compared to roscovitine or IR treatment alone. Meanwhile, in the co-treatment group, the percentage of cells with the active form of caspase-3 was markedly increased, while roscovitine or IR alone had little effect. Roscovitine decreased S phase cells when used alone or in sequential combination with IR. Furthermore, this combination treatment blocked DNA repair process after IR, indicated by down regulation of Ku70 and Ku80 proteins, while the singly used treatment did not. Taken together, these results suggest that roscovitine has the potential to act as a radio-sensitizer in A549 cells by promoting caspase-3 activity and increasing apoptosis, affecting cell cycle distribution and impairing DNA repair process.
- 日本放射線影響学会の論文
- 2008-09-16
著者
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ZHANG Tao
Department of Chemistry, Faculty of Engineering, Mie University
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Zhou Yong-an
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University
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WANG Xiao-ping
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University
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GU Zhong-ping
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University
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LI Xiao-fei
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University
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ZHANG Feng
Department of Cardiology, Zhongshan Hospital, Fudan University
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Li Xiao-fei
中華人民共和国
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Li Xiao-fei
Dep. Of Thoracic Surgery Tangdu Hospital Fourth Military Medical Univ.
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Wang Xian-ni
Dep. Of Neurology Tangdu Hospital Fourth Military Medical Univ.
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Wang Xian-ni
中華人民共和国
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Gu Zhong-ping
Dep. Of Thoracic Surgery Tangdu Hospital Fourth Military Medical Univ.
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Wang Xiao-ping
Department Of Nutrition And Food Hygiene School Of Radiation Medicine And Public Health Medical Coll
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MEI Qi-Bing
Department of Pharmacology, School of Pharmacy, Fourth Military Medical University
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HAN Yong
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University
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CHENG Qing-Shu
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University
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Cheng Qing-shu
Department Of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University
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Zhang Tao
Department Of Advanced Systems Control Engineering Graduate School Of Science And Engineering Saga U
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Mei Qi-bing
Department Of Pharmacology School Of Pharmacy Fourth Military Medical University
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Mei Qi-bing
Department Of Pharmacology The Fourth Military Medical University
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Zhang Tao
Department Of Thoracic Surgery Tangdu Hospital Fourth Military Medical University
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Li Xiao-fei
Department Of Thoracic Surgery Tangdu Hospital Fourth Military Medical University
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Gu Zhong-ping
Department Of Thoracic Surgery Tangdu Hospital Fourth Military Medical University
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Zhou Yong-an
Department Of Thoracic Surgery Tangdu Hospital Fourth Military Medical University
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Han Yong
Department Of Endocrinology Provincial Hospital Affiliated To Shandong University
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Han Yong
Department Of Thoracic Surgery Tangdu Hospital The Fourth Military Medical University
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Zhang Feng
Department Of Pharmacology The Fourth Military Medical University
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ZHANG Feng
Department of Bioresource Science, United Graduate School of Agricultural Science, Iwate University
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