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Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro

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Chinese Medical Journal 2008年第18期121卷 1830-1837页

作者： XU Qing-yong GAO Yuan LIU Yan YANG Wei-zhi XU Xiang-ying Department of radiation Oncology Cancer Hospital Harbin Medical University Harbin Heilongjiang 150081 China Department of Biochemistry Harbin Medical University Harbin Heilongjiang 150086 China Department of Radiobiology Cancer Institute (Hospital) Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 China

Background Radiotherapy plays a critical role in the management of non-small cell lung cancer （NSCLC）. This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation （FIR） by cDNA microarray. Methods The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes. Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction （Q-RT-PCR）. Results Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair （DDB2）, extracellular matrix （LOX）, cell adhesion （CDH2）, and apoptosis （CRYAB）. Down-regulated genes were associated with angiogenesis （GBP-1）, immune response （CD83）, and calcium signaling pathway （TNNC1）. Subsequent validation of selected eleven genes （CD24, DDB2, IGFBP3, LOX, CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83） by Q-RT-PCR was consistent with microarray analysis. Conclusions fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.

关键词： radioresistance cDNA microarray non-small cell lung cancer fractionated ionizing radiation

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