Cai Yong, Zhao Helon, Lee Hoyun
Department of Radiation Oncology, Peking University School of Oncology, Beijing 100036, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2006 Aug 18;38(4):411-4.
To study the genes associated with CQ (Chloroquine) increased radiosensitivity in radioresistant MDA-MB 231 cells.
The survival curve of MDA-MB 231 breast cancer cells was establish in the presence or absence of CQ after irradiation by colongenic assay. The relationship between certain protein expressions (MLH1, ERCC1, PARP, RAD51, XRCC4) and CQ increased radiosensitivity in radioresistant MDA-MB 231 cells was examined by Western blot method. The genes which are associated with CQ increased radiosensitivity were studied by microarray analysis.
CQ increased deaths of parental MDA-MB 231 cells, radiosensitive MDA-MB 231 cells and radioresistant MDA-MB 231 cells were compared with those of the CQ-untreated control cells after irradiation, and the Radiation Potentiation Factor were 1.21-1.23. The expression of ERCC1 in the presence and absence of CQ in the radioresistant cells was significantly higher than that of sham-irradiated control cells by Western blot method. After irradiation, RAD51 level was increased up to 3-hour radiation and then gradually reduced. The expression of MLH1 was lower in 24 hours than that of other time points after irradiation. There were no differences on the expressions of MLH1, ERCC1, RAD51 in cells with and without CQ, which suggested that these genes weren't correlated with CQ increased radiosensitivity. XRCC4 and PARP levels were not changed by irradiation. Microarray analysis showed that TNP3, FRIH, CA21, ADTA genes might be related to CQ increased radiosensitivity in radioresistant cells.
CQ can increase radiosensitivity in radioresistant MDA-MB 231 breast cancer cells. It is not related to MLH1, ERCC1, PARP, RAD51, XRCC4 genes. TNP3 may play an important role in CQ increase radiosensitivity in radioresistant MDA-MB 231 breast cancer cells.
研究与氯喹（CQ）增加耐辐射MDA-MB 231细胞放射敏感性相关的基因。
通过克隆形成试验，在有或无CQ存在的情况下，建立MDA-MB 231乳腺癌细胞的存活曲线。采用蛋白质免疫印迹法检测某些蛋白质表达（MLH1、ERCC1、PARP、RAD51、XRCC4）与CQ增加耐辐射MDA-MB 231细胞放射敏感性之间的关系。通过基因芯片分析研究与CQ增加放射敏感性相关的基因。
CQ增加了亲本MDA-MB 231细胞的死亡，将耐辐射MDA-MB 231细胞、放射敏感MDA-MB 231细胞与照射后未用CQ处理的对照细胞进行比较，放射增敏因子为1.21 - 1.23。蛋白质免疫印迹法显示，耐辐射细胞在有和无CQ存在时，ERCC1的表达均显著高于假照射对照细胞。照射后，RAD51水平在照射3小时内升高，然后逐渐降低。照射后24小时MLH1的表达低于其他时间点。有或无CQ的细胞中MLH1, ERCC1, RAD51的表达无差异，这表明这些基因与CQ增加放射敏感性无关。照射未改变XRCC4和PARP水平。基因芯片分析表明，TNP3、FRIH、CA21、ADTA基因可能与CQ增加耐辐射细胞的放射敏感性有关。
CQ可增加耐辐射MDA-MB 231乳腺癌细胞的放射敏感性。这与MLH1、ERCC1、PARP、RAD51、XRCC4基因无关。TNP3可能在CQ增加耐辐射MDA-MB 231乳腺癌细胞放射敏感性中起重要作用。
