地拉罗斯联合顺铂对非小细胞肺癌细胞增殖及凋亡的影响  

The effect of combination treatment using iron chelator deferasirox and cisplatin on proliferation and apoptosis in non-small cell lung cancer

作　　者：袁婷[1] 梁吉祥[2] 张斌[1] 汪蓓蕾[1] 张欣[1] 郭刚[1] 张瑞[1] 

机构地区：[1]天津医科大学代谢病医院内分泌研究所、卫生部激素与发育重点实验室,300070 [2]天津医科大学第二医院

出　　处：《天津医药》2015年第2期137-141,共5页Tianjin Medical Journal

摘　　要：目的探讨铁鳌合剂地拉罗斯及其联合顺铂对肺腺癌A549细胞增殖、凋亡的影响,为寻找肺癌有效的治疗途径提供依据。方法常规传代细胞培养方法培养肺腺癌细胞A549,以不同浓度的地拉罗斯、地拉罗斯联合顺铂干预细胞生长一定时间。在倒置显微镜下观察A549的生长抑制特征;MTT法检测细胞的增殖抑制状况;DAPI、AO/EB染色观察细胞凋亡的形态学变化;Annxin V-FITC/PI双染流式细胞术定量测定细胞凋亡状况。结果 A549细胞经不同浓度的药物作用一定时间以后,在倒置显微镜下可见随药物浓度和时间的增加,细胞数明显减少,细胞相互分散,贴壁细胞出现皱缩变小折光性差;MTT检测显示,细胞增殖抑制率随药物浓度的增加和作用时间的延长呈现上升趋势,即剂量效应关系及时间效应关系;DAPI、AO/EB染色法观察到细胞凋亡的形态学变化,即细胞发生染色质凝集,核固缩等典型的凋亡形态特征;流式细胞术检测显示,细胞的凋亡率随药物浓度的增加而升高,联合用药促细胞凋亡显著。结论铁鳌合剂地拉罗斯具有抗肺癌细胞A549增殖的能力,促进肿瘤细胞凋亡,其与顺铂联合可增强癌细胞耐受性,降低顺铂的用量及其不良反应。Objective To investigate the combination effect using iron chelators deferasirox and cisplatin on A549 cellproliferation and apoptosis and to provide evidences to explore an effective way to treat lung cancer. Methods Lung adeno-carcinoma cells were cultured by conventional way, with administration of different concentrations of deferasirox and cisplat-in. Cell growth inhibition was observed under an inverted microscope. Proliferation inhibition was evaluated by MTT assay.Morphological changes of cell apoptosis was detected using DAPI,AO/EB straning and flow cytometry. Results After a cer-tain time of incubation with different concentrations of the combined drugs,the cell number reduce significantly, which wascounted under invert microscope. Cells were dispersed with each other and adherent cells appear shrunken and poor in re-fractivity. MTT assay showed that inhibition of cell proliferation was in a concentration-time-dependent manner. Chromatincondensation, nuclear condensation and other typical apoptotic morphology were detected after DAPI and AO/EB straning.Flow cytometry showed that apoptosis increased with rising drug concentration. So combination therapy was significantlypro-apoptotic. Conclusion Deferasirox has the ability to inhibit proliferation of A549 cells and can promote tumor cellapoptosis and enhances cancer cell tolerance when combined with cisplatin. It can also reduce the amount and toxicity of cis-platin. It provides a basis for finding an effective way to treat lung cancer.

关 键 词：癌 非小细胞肺 铁螯合剂 顺铂 细胞增殖 细胞凋亡 地拉罗斯 

分 类 号：R734.2[医药卫生—肿瘤]