| 孟兰,丁西平,胡群力,殷实,沈干,胡世莲.5-氮杂-2-脱氧胞苷通过上调MGMT表达增加5-氟尿嘧啶联合紫杉醇的化疗敏感性[J].中国临床保健杂志,2017,20(5):584-588. |
| 5-氮杂-2-脱氧胞苷通过上调MGMT表达增加5-氟尿嘧啶联合紫杉醇的化疗敏感性 |
| 5-Aza-2′-deoxycitydine enhances the anti-tumor effect of 5-FU combined paclitaxel against gastric cancer through up-regulation MGMT |
| 投稿时间：2017-07-01 |
| DOI：10.3969/J.issn.1672-6790.2017.05.028 |
| 中文关键词: 胃肿瘤 氟尿嘧啶 紫杉烷类 脱氧胞苷核苷酸类 药物相互作用 |
| 英文关键词: Stomach neoplasms Fluorouracil Taxoids Deoxycytosine nucleotides Drug interactions〖FL |
| 基金项目:国家自然科学基金(8107180)；肿瘤免疫与营养治疗安徽省重点实验室绩效项目(1606c08236)；安徽省科技攻关项目(1501041142) |
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| 中文摘要: |
| 目的 研究5-氮杂-2-脱氧胞苷(5-Aza-dC)与传统化疗药物5-氟尿嘧啶联合紫杉醇(5-FU+PTX)对人胃癌细胞生长的影响,探讨5-Aza-dC抗肿瘤的机制。方法 培养人胃癌细胞株MKN-45,分为对照组、5-Aza-dC组、5-FU+PTX组和5-Aza-dC+5-FU+PTX组,利用CCK-8细胞增殖检测试剂盒、流式细胞术检测各组细胞的增殖和凋亡情况,利用RT-PCR和Western blot方法分别检测各组胃癌细胞的MGMT基因mRNA与蛋白表达,及凋亡蛋白cleaved caspase-3的表达。结果 5-Aza-dC及5-FU联合紫杉醇均可抑制MKN-45细胞的生长,48 h细胞存活率分别为(71.60±5.77,7.00±6.09)%,与5-FU+PTX组比较,三药联合使用后效果更明显(42.85±2.29)%,P=0.02；5-Aza-dC及5-FU联合紫杉醇组细胞凋亡率[(7.33±0.34)%,(13.06±1.67)%]及凋亡蛋白cleaved caspase-3水平[(43.00±4.00)%,(45.67±4.50)%]均增加,三药联合用药组凋亡率[(17.31±1.05)%]和cleaved caspase-3水平[(174.67±6.50)%]的表达更高。与对照组抑癌基因MGMT mRNA和蛋白表达量[(23.10±2.15)%、(10.47±1.39)%]比较,5-Aza-dC单独处理的MKN-45细胞MGMT基因mRNA(56±5.57)%及蛋白表达水平(20.33±5.50)%均升高,三药联合用药组MGMT升高程度更加明显[(75.67±6.50)%,(174.67±6.50)%],P＜0.001,而5-FU联合紫杉醇组未发现明显变化。结论 5-Aza-dC可以有效抑制胃癌细胞的生长,它与化疗药物5-FU和紫杉醇联合应用时抗肿瘤效应更加明显。 |
| 英文摘要: |
| Objective To explore the potential effects of 5-Aza-2′-deoxycitydine (5-Aza-dC),5-FU combined Paclitaxel (PTX) for the treatment of patients with gastric cancer and its mechanism.Methods The inhibitory effects of 5-Aza-dC and/or 5-FU combined PTX on MKN-45 cell proliferation were assayed by using CCK-8 kit.The apoptosis of MKN-45 cell was determined by Annexin V-FITC/PI staining method.MGMT mRNA in vitro was determined by RT-PCR,and the cleaved caspase-3 and MGMT protein expression were detected by western blotting.Results The cell growth of human gastric carcinoma cell line MKN-45 was significantly inhibited by 5-Aza-dC(71.60±5.77 )% or 5-FU combined PTX (57.00±6.09)%,the combination of 5-Aza-dC and 5-FU+PTX(42.85±2.29)% resulted in a better inhibition.Compared with the control group,5-Aza-dC and 5-FU combined PTX group induced the apoptosis of MKN-45 cells[(7.33±0.34)%,(13.06±1.67)%],with the apoptotic rate significantly higher in the combination group than that in single drug treatment group(17.31±1.05)%,as well as indicated in cleaved caspase-3 protein expression.Exposure of MKN-45cell to 5-Aza-dC alone resulted in a significant increase in the expression levels of MGMT mRNA and protein[(56.00±5.57)%,(20.33±5.50)%],and the effects were consequently more pronounced in the combined group[(75.67±6.50)%,(174.67±6.50)%],P＜0.001.Conclusion 5-Aza-dC can inhibit cell proliferation and induce apoptosis in human gastric carcinoma.Moreover,5-Aza-dC combined with 5-FU and PTX is more efficient than either 5-Aza-dC or 5-FU combined PTX alone. |
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