| 全反式维甲酸增强顺铂对A549 细胞化疗敏感性及对Survivin mRNA 和COX-2 mRNA表达的影响 |
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| 引用本文： | 王学雷,陈小华,路阳,郭成山,马骥,高万军,葛言红.全反式维甲酸增强顺铂对A549 细胞化疗敏感性及对Survivin mRNA 和COX-2 mRNA表达的影响[J].中国肿瘤临床,2010,37(9):490-494. |
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| 作者姓名： | 王学雷 陈小华 路阳 郭成山 马骥 高万军 葛言红 |
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| 作者单位： | 作者单位:齐鲁石化医院集团中心医院肿瘤科(山东省淄博市255400);①山东大学第二医院血液-肿瘤中心 |
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| 摘 要： | 目的:体外观察全反式维甲酸（all-trans retinoic acid ，ATRA）增强顺铂（cisplatin，DDP ）对人类非小细胞肺癌细胞株A549 细胞的增殖抑制及对凋亡抑制蛋白Survivin mRNA和环氧化酶-2（cyclooxygenase- 2，COX-2）mRNA 表达的影响。方法:应用不同浓度组DDP（0.5、5、50mg/L）、ATRA（0.1、1、10μ mol/L）以及联合用药组（ATRA 1 μ mol/L，DDP 5mg/L），处理肺腺癌细胞株A549 细胞，采用四甲基偶氮唑盐（MTT）比色法观察不同浓度DDP 组、不同浓度ATRA 组及联合用药组对A549 细胞生长的影响；应用实时荧光定量聚合酶链反应（real-time polymerase chain reaction ，RT-PCR）检测DDP 组、ATRA 组及联合用药组处理前后A549 细胞中Survivin mRNA和COX-2 mRNA 表达变化；应用流式细胞术观察DDP 组、ATRA 组及联合用药组处理前后细胞凋亡率。结果:与空白对照组相比，单独应用DDP 、ATRA 处理A549 细胞均诱导细胞凋亡，且呈浓度依赖性。与单独应用DDP 的作用相比，联合用药组可更显著抑制A549 的增殖，增加细胞的凋亡率（P<0.05），并增强对A549 细胞Survivin mRNA和COX-2 mRNA表达的抑制作用（P<0.05）；并且，流式细胞术测定结果显示联合用药组的早期凋亡率（7.37± 3.83）% 、中晚期凋亡率（34.37±2.08）% 、继发性坏死率（7.44± 0.46）% 均较单独应用DDP 组高（3.55± 0.75）% 、（6.62± 0.33）% 、（3.03± 0.05）% ，P 均<0.05。结论:全反式维甲酸能够明显提高非小细胞肺癌对顺铂的敏感性，其机制可能与抑制非小细胞肺癌细胞Survivin mRNA和COX-2 mRNA 的表达有关。
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| 关 键 词： | 全反式维甲酸 顺铂 非小细胞肺癌 环氧化酶-2 Survivin |
| 收稿时间： | 2009-12-07 |
All-trans Retinoic Acid Can Enhance Chemosensitivity of Human Non-Small Cell Lung Cancer Cell Line A549 to Cisplatin and Suppress Expression of mRNA and Cox-2 mRNA in vitro |
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| Affiliation: | 1Department of Oncology, Central Hospital of Qilu Petrochemical Group, Zibo 274000, China |
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| Abstract: | Objective:To investigate the influence of cisplatin (DDP) combined with all-trans retinoic acid (ATRA) on the growth and apoptosis of human non-small cell lung cancer A549 cell line and on the expression of Survivin mRNA and COX-2 mRNA in this cell line in vitro. Methods:Different concentrations of DDP (0.5mg/L, 5mg/L, and 50mg/L), different concentrations of ATRA (0.1 μ mol /L, 1 μ mol /L, and 10μ mol /L) and DDP combined wi th ATRA (DDP 5mg/L and ATRA1 μ mol /L) were used in cultures for the pulmonary carcinoma A 549 cell line in different groups. The influence on A 549 growth induced by different concentrations of DDP, different concentrations of ATRA, and DDP combined with ATRA were analyzed by MTT assay. Expression of Survivin mRNA and COX- 2 mRNA levels in the A549 cells were detected by R-T PCR before and after treatment. Flow cytometry (Annexin V-FITC/PI Staining Methods) was used to determine the apoptosis index of the A 549 cells before and after treatment. Results: DDP alone or ATRA alone was found to inhibit the proliferation of the A549 cells ( P<0.05), and the apoptotic effect was increased in a concentration-dependent manner (P<0.05). Compared with DDP alone, DDP combined with ATRA significantly inhibited the proliferation of the A 549 cells ( P<0.05), increased the apotosis rate of the cells and suppressed Survivin mRNA and COX-2 mRNA expression in the cells ( P<0.05). Flow cytometry results showed that the early apoptosis rate, middle and late apoptosis rate and secondary necrosis rate in the DDP combined with ATRA group were (7.37± 3.83)%, (34.37± 2.08)%, and (7.44± 0.46)%, respectively, higher than those of the DDP group ( 3.55± 0.75)%, (6.62± 0.33)%, and (3.03± 0.05)%, P<0.05]. Conclusion:ATRA can significantly increase the chemosensitivity of human non-small cell lung cancer cells to DDP. The mechanism may be related to inhibition of Survivin mRNA and COX-2 mRNA expression. |
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| Keywords: | Survivin |
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