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为探讨DNA去甲基化试剂5-氮杂-2′-脱氧胞苷(5-aza-2′-deoxycytidine,5-Aza-CdR)对三维(3D)培养模式下的肺腺癌细胞A549辐射敏感性的作用,开展了系列实验。使用不同浓度5-Aza-CdR处理单层(2D)A549细胞72 h后,MTT法检测其对A549细胞的增殖抑制作用。选取低浓度(2,5μmol/L)5-Aza-CdR预处理2D和3D培养的A549细胞72 h,X射线分别辐照1,2,4,6 Gy,检测微核形成率和克隆存活。实验结果显示,不同浓度的5-Aza-CdR均能抑制2D的A549细胞增殖,且呈剂量依赖性。5μmol/L药物预处理2D与3D细胞并联合辐照后诱导的细胞微核形成率均显著高于相应的对照组,并且细胞存活率显著降低。不过,较低浓度5-Aza-CdR(2μmol/L)预处理的3D培养A549细胞4,6 Gy辐照后微核数目较未用药处理组显著增加,克隆存活率较未用药组显著降低(P<0.05),而在2D培养A549细胞中未观测到上述现象。研究结果表明,5-Aza-CdR能抑制A549细胞增殖,3D培养A549细胞药物预处理更能增加其辐射敏感性。结果暗示,为减少对正常细胞的毒性作用,在临床放疗中,可低剂量使用5-Aza-CdR,实现肿瘤的有效靶向治疗。
To investigate the effect of DNA demethylating agent 5-aza-2’-deoxycytidine (5-Aza-CdR) on lung adenocarcinoma A549 cells in three-dimensional The role of sensitivity, conducted a series of experiments. The monolayers of A549 cells were treated with 5-Aza-CdR for 72 h. The proliferation of A549 cells was detected by MTT assay. A549 cells pretreated with 5-Aza-CdR at low concentration (2,5μmol / L) for 2D and 3D for 72 h were irradiated with 1, 2, 4 and 6 Gy respectively by X-ray. The rate of micronuclei formation and clonality were detected. The results showed that different concentrations of 5-Aza-CdR can inhibit the proliferation of 2D A549 cells in a dose-dependent manner. The micronucleus formation rate induced by 5μmol / L pretreatment of 2D and 3D cells combined with irradiation was significantly higher than that of the corresponding control group, and the cell survival rate was significantly decreased. However, the number of micronuclei in the 4,6 Gy irradiated A549 cells pretreated with 5-Aza-CdR (2μmol / L) was significantly increased compared with that of the untreated A549 cells. The survival rate of the clones was significantly lower than that of the untreated group P <0.05), whereas no such phenomenon was observed in 2D cultured A549 cells. The results showed that 5-Aza-CdR could inhibit the proliferation of A549 cells, and the drug-pretreatment of A549 cells in 3D could increase its radiation sensitivity. The results suggest that in order to reduce the toxic effects on normal cells, 5-Aza-CdR may be used in low doses in clinical radiotherapy to achieve effective targeted therapy of tumors.