| 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 |
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| 引用本文： | 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. DOI: 10.3969/J.issn.1672-6790.2017.05.028 |
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| 作者姓名： | 孟兰 丁西平 胡群力 殷实 沈干 胡世莲 |
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| 作者单位： | 1. 安徽医科大学附属省立医院,合肥230001;安徽省老年医学研究所;肿瘤免疫与营养治疗安徽省重点实验室;2. 安徽医科大学附属省立医院,合肥,230001;3. 安徽医科大学附属省立医院,合肥230001;安徽省老年医学研究所 |
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| 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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| 摘 要： | 目的研究5-氮杂-2-脱氧胞苷(5-Aza-d C)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-d C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-d C组、5-FU+PTX组和5-Aza-d C+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m RNA与蛋白表达,及凋亡蛋白cleaved caspase-3的表达。结果 5-Aza-d C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±5.77,57.00±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-d C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 m RNA和蛋白表达量[(23.10±2.15)%、(10.47±1.39)%]比较,5-Aza-d C单独处理的MKN-45细胞MGMT基因m RNA(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-d C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。
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| 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 |
| 收稿时间： | 2017-07-01 |
5-Aza-2'-deoxycitydine enhances the anti-tumor effect of 5-FU combined paclitaxel against gastric cancer through up-regulation MGMT |
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| Meng Lan,Ding Xiping,Hu Qunli,Yin Shi,Shen Gan,Hu Shilian. 5-Aza-2'-deoxycitydine enhances the anti-tumor effect of 5-FU combined paclitaxel against gastric cancer through up-regulation MGMT[J]. Chinese Journal of Clinical Healthcare, 2017, 20(5): 584-588. DOI: 10.3969/J.issn.1672-6790.2017.05.028 |
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| Authors: | Meng Lan Ding Xiping Hu Qunli Yin Shi Shen Gan Hu Shilian |
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| Abstract: | 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 RTPCR,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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| Keywords: | Stomach neoplasms Fluorouracil Taxoids Deoxycytosine nucleotides Drug interactions |
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