ZHOU Zhi-rui,ZHU Xiao-dong,ZHAO Wei,et al.Contribution of autophagy inhibitor to radiation sensitization in nasopharyngeal carcinoma cells[J].Chinese Journal of Radiological Medicine and Protection,2012,32(5):449-454 |
Contribution of autophagy inhibitor to radiation sensitization in nasopharyngeal carcinoma cells |
Received:June 02, 2012 |
DOI:10.3760/cma.j.issn.0254-5098.2012.05.001 |
KeyWords:Autophagy Nasopharyngeal carcinoma Radiosensitivity Chloroquine phosphate Rapamycin |
FundProject:国家自然科学基金(81160285);广西壮族自治区自然科学基金(桂科自2010gxnsfa013240) |
Author Name | Affiliation | E-mail | ZHOU Zhi-rui | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | ZHU Xiao-dong | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | zhuxdonggxmu@yahoo.cn | ZHAO Wei | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | QU Song | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | PAN Wen-yan | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | GUO Ya | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | SU Fang | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | | LI Xiao-yu | Department of Radiotherapy, Cancer Hospital of Guangxi Medical University Symbolf@@ Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning 530021, China | |
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Abstract:: |
Objective To investigate the role of autophagy in radiation-induced death response of human nasopharyngeal carcinoma cells.Methods MTT method was used to detect cell viability of CNE-2 cells in different time after irradiation. Clonogenic survival assay was used to evaluate the effect of autophagy inhibitor (chloroquine phosphate) and autophagy inductor (rapamycin) on radiosensitivity of nasopharyngeal carcinoma cells. Cell apoptosis was assessed by flow cytometry. The expressions of LC3 and P62 were measured with Western blot. Cell ultrastructural analysis was performed under an electron microscope. Results Irradiation with 10 Gy induced a massive accumulation of autophagosomes accompanied with up-regulation of LC3-Ⅱ expression in CNE-2 cells. Compared with radiation alone, chloroquine phosphate (CDP) enhanced radiosensitivity significantly by decreasing cell viability (F=25.88,P<0.05), autophagic ratio(F=105.15,P<0.05), and LC3-Ⅱ protein level(F=231.68,P<0.05), while up-regulating the expression of P62(F=117.52,P<0.05). Inhibition of autophagy increased radiation-induced apoptosis(F=143.72,P<0.05). Rapamycin (RAPA) also significantly decreased cell viability, but increased autophagic ratio and LC3-Ⅱ protein level while down-regulated the expression of P62. Induction of autophagy increased radiation-induced apoptosis(F=167.32, P<0.05). Conclusions Blockage of autophagy with CDP could enhance radiosensitivity in human nasopharyngeal carcinoma cells, suggesting that inhibition of autophagy could be used as an adjuvant treatment to nasopharyngeal carcinoma. |
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