| Ras和磷酸化ERK信号通路参与三氧化二砷逆转耐药作用机制的研究 |
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| 引用本文： | 刘宝玲,赵园园,于丽,何信佳,张碧媛. Ras和磷酸化ERK信号通路参与三氧化二砷逆转耐药作用机制的研究[J]. 中国肿瘤临床, 2013, 0(9): 505-508. DOI: 10.3969/j.issn.1000-8179.2013.09.004 |
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| 作者姓名： | 刘宝玲 赵园园 于丽 何信佳 张碧媛 |
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| 作者单位： | 青岛大学医学院附属医院肿瘤科（山东省青岛市266000） |
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| 摘 要： | 目的 体外实验研究三氧化二砷(As2O3)对人胃癌阿霉素耐药细胞株(SGC7901/ADM)的逆转耐药机制。 方法 MTT法检测磷酸化ERK(p-ERK)激动剂G-CSF作用前后As2O3的逆转耐药倍数; 免疫细胞化学法测定As2O3及G-CSF作用前后SGC7901/ADM细胞内Ras和p-ERK的变化; 流式细胞仪测定G-CSF和As2O3干预后SGC7901/ADM的细胞周期和凋亡率。 结果 SGC7901/ADM对ADM耐药, As2O3可逆转耐药, 其中0.5μmol/L As2O3作用48 h后逆转耐药倍数约为6.29。G-CSF干预后, 逆转耐药倍数降至4.72;SGC7901/ADM中Ras表达高于亲本细胞株SGC7901/S, 而p-ERK无明显差异, As2O3可下调Ras及p-ERK的表达。G-CSF干预后, As2O3下调Ras及p-ERK表达的能力较干预前显著降低。0.1μmol/L和0.5μmol/L As2O3组的G0~G1期细胞比例和凋亡率均显著高于各个对照组; G-CSF干预后同一剂量的As2O3组G0~G1期细胞及凋亡率较干预前均显著降低。 结论 As2O3可逆转人胃癌耐药细胞株SGC7901/ADM对ADM的耐药作用, 其机制与下调Ras/p-ERK信号传导通路中Ras、磷酸化ERK的表达有关。
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| 关 键 词： | 三氧化二砷 多药耐药 Ras 磷酸化ERK |
| 收稿时间： | 2012-09-24 |
Study on the role of Ras/p-ERK signaling pathway in the reversing effect of As2O3 on multi-drug-resistance |
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| Affiliation: | Qingdao University, Qingdao 266000, ChinaDepartment of Oncology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266000, China |
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| Abstract: | Objective The aim of this in vitro study is to assess the reversing effects of arsenic trioxide(As2O3) on multi-drug-resistance(MDR) of SGC7901/adriamycin(ADM) and determine the molecular mechanism associated with Ras/p-ERK downregulation in human gastric cancer cells. Methods The reversing effects of As2O3 before and after the treatment with an ERK agonist were determined by methyl thiazolyl tetrazolium assay.The molecular mechanism involved was further studied by examining the expressions of Ras and phosphorylated p-ERK by immunocytochemical assay.The process was repeated in pre-and post-intervention of As2O3 and granulocyte colony stimulating factor(G-CSF), respectively.Changes in the cell cycle and apoptotic rates were determined by flow cytometry. Results SGC7901/ADM was resistant to ADM, and As2O3 could reverse the drug resistance.After the treatment of As2O3 at a dose of 0.5 μmol/L for 48 h, the the multiple of reversed drug resistance was about 6.29 approximately, which was greater compared with that of the normal cells.After administration of As2O3, the IC50decreased dramatically, which shows that As2O3 could reverse MDR.After the G-CSF intervention, the multiple of the reversing effects was only 4.72.Immunocytochemical assay showed higher expressions of Ras in SGC7901/ADM than in the parental cell line SGC7901/S.No obvious difference in the p-ERK expressions of these cell lines was observed. As2O3 could decrease both Ras and p-ERK expressions(q-test, P < 0.01).After pre-treatment with the ERK agonist, Ras and p-ERK expressions decreased(t-test, P < 0.01).Flow cytometry indicated that the proportion of G0-G1 cells and apoptosis rate were higher in the As2O3 –treated group(0.1 and 0.5 μmol/L) than in the control groups.And apoptotic rate of both the cells significantly decreased in the As2O3 group of the same dose after treatment of G-CSF. Conclusion As2O3 can reduce the MDR of gastric cancer in vitro via the Ras/p-ERK signaling transduction pathway. |
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| Keywords: | arsenic trioxide MDR ras p-ERK |
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