| 王燕泽,崔 璨,张红梅.PDTC对胃癌细胞MKN-45 p53异构体表达的影响及其生物学意义[J].中国肿瘤,2017,26(2):156-160. |
| PDTC对胃癌细胞MKN-45 p53异构体表达的影响及其生物学意义 |
| Effect of PDTC on Expression of p53 Isoforms in Gastric Cancer Cell Line MKN-45 and Its Biological Significance |
| 投稿时间：2016-05-15 |
| DOI：10.11735/j.issn.1004-0242.2017.02.A016 |
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| 中文关键词: p53β Δ133p53 NF-κB p65 胃癌 吡咯烷二硫代氨基甲酸 顺铂 |
| 英文关键词:p53β Δ133p53 NF-κB p65 gastric cancer pyrrolidine dithiocarbamate (PDTC) cisplatin |
| 基金项目:山东省优秀中青年科学家科研奖励基金(BS2010SW034) |
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| 中文摘要: |
| 摘 要：［目的］ 探讨核因子-κB(NF-κB) 抑制剂吡咯烷二硫代氨基甲酸(PDTC)对胃癌细胞MKN-45 p53异构体表达的影响及其生物学意义。 ［方法］ 不同浓度的PDTC（25、50、75μmol/L）单独及联合顺铂(4μg/ml)作用于胃癌细胞MKN-45，采用细胞增殖/毒性检测试剂盒(CCK-8试剂盒)检测细胞增殖抑制率；实时荧光定量多聚酶链反应(RT-PCR)检测p53β、Δ133p53及NF-κB p65在mRNA水平的表达情况。［结果］ CCK-8结果显示，PDTC(25、50、75μmol/L)单独作用时能抑制MKN-45细胞生长，抑制率分别为4.95%、12.20%、21.28%，差异有统计学意义（P＜0.0001）；当与顺铂（4μg/ml）联合时，MKN-45细胞增殖抑制率随PDTC浓度的增加而增加，且高于单独顺铂组，差异有统计学意义（P＜0.001）。RT-PCR结果显示，当用不同浓度PDTC (25、50、75μmol/L) 预处理2h后再加入顺铂（4μg/ml），MKN-45细胞中p53β mRNA的表达差异无统计学意义（P=0.04），而Δ133p53和p65 mRNA的表达随PDTC浓度的增加而降低，且低于顺铂单独组，差异有统计学意义（P＜0.0001）。Pearson相关性分析显示，p65与p53β mRNA表达无相关性（r=0.072，P=0.798），p65与Δ133p53 mRNA表达呈正相关（r=0.814，P＜0.0001）。 ［结论］ NF-κB 抑制剂PDTC可以抑制MKN-45细胞的生长，也可以增强顺铂对该细胞的生长抑制效应，Δ133p53异构体可能是NF-κB-p53对话的关键分子。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the effect of the nuclear factor-κB(NF-κB) inhibitor pyrrolidine dithiocarbamate(PDTC) on the expression of p53 isoforms in gastric cancer MKN-45 cells and its biological significance. ［Methods］ Different concentrations of PDTC (25，50，75μmol/L) alone or in combination with cisplatin (4μg/ml) were used to treat gastric cancer MKN-45 cells. The inhibition rate of MKN-45 cells was determined by cell proliferation/toxicity testing kits(CCK-8 assay). The mRNA expressions of p53β，Δ133p53 and NF-κB p65 were determined by real-time polymerase chain reaction(RT-PCR). ［Results］ CCK-8 assay showed that PDTC(25，50，75μmol/L) inhibited the growth of gastric cancer MKN-45 cells with an inhibition rate of 4.95%，12.20% and 21.28% respectively(P＜0.0001). When combined with cisplatin，the inhibition rate of PDTC was higher than PDCT alone(P＜0.001). RT-PCR showed that，when cisplatin(4μg/ml) was added in PDTC-pretreated MKN-45 cells，the expressions of Δ133p53 and p65 mRNA were reduced and lower than that in cells treated by cisplatin alone(P＜0.0001)；however，there were no significant changes of p53β mRNA expression(P=0.04). Pearson correlation analysis showed that there was no correlation between mRNA expression of p65 and p53β（r=0.072，P=0.798）.The mRNA expression of p65 was positively correlated with Δ133p53(r=0.814，P＜0.0001）. ［Conclusion］ NF-κB inhibitor PDTC can inhibit the growth of gastric cancer MKN-45 cells，and enhance inhibitory effect of cisplatin. The results indicate that Δ133p53 rather than p53β isoforms might be a key molecule of the NF-κB-p53 interaction. |
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