地塞米松降低肺癌细胞对顺铂化疗敏感性的机制与分析

Mechanism and analysis of dexamethasone in reducing cis-Dichlorodiammineplatinum chem otherapy sensitivity of lung cancer cells

目的探讨地塞米松对顺铂治疗肺癌时诱导的细胞凋亡的影响及其机制。方法将人肺癌细胞A549分为单纯顺铂组、顺铂联合不同浓度地塞米松处理组(联合组),分别检测处理后细胞的增殖情况。采用RT-PCR检测DNA损伤信号通路及细胞NF-κB信号通路上的相关基因p53和cyclin D1的表达情况。结果与单纯顺铂组相比,联合组提高了肿瘤细胞的存活率,抑制了由顺铂诱导的细胞凋亡现象。联合处理后的肿瘤细胞中关键因子抑癌基因p53表达上调和肿瘤细胞中原癌基因cyclinD1的表达下调的效应均受到抑制,从而表现出肿瘤细胞对化疗药物顺铂失敏的现象。结论地塞米松通过干扰化疗药物对肿瘤细胞的抑制作用而降低了化疗药物顺铂对肺癌细胞的敏感性,这其中部分原因是由于下调了p53所致。提示临床肿瘤治疗方案中,糖皮质激素与抗癌药物的联合使用应当慎重。

Objective It is to approach the influence and mechanism of dexamethasone （DEX） on lung cancer cells sensitivity to cis-Dichlorodiammineplatinum （DDP）.Methods Human lung cancer cell A549 was divided into DDP group and DDP combined with difference concentration DEX groups （combined group）,and treated with DDP in the presence or absence of different concentration of DEX.The number of viable cell and the cell proliferation was measured by the MT-assay; Expression of DNA damage signaling and cellular NF-κB signaling pathway related genes p53 and cyclin D1 were detected by RT-PCR.Results Compared with DDP group,the survival rate of tumor cells in combined group was improved,and the apoptosis reduced by cisplatin was inhibited.After combined treatment of tumor cells,the expression of key factor gene of DNA damage signaling pathway-p53 was suppressed,and the expression of cyclinD1-the key gene of NF-kB signaling pathway was upregulated.Con^usion DEX can interferes the depressant effect of chemotherapy drugs on tumor cells and reduce the sensitivity of lung cancer cells for chemotherapy,which is due in part to cut p53 induced.So the combined use of glucocorticoid and anticancer drugs should be careful in clinical tumor treatment.