国际肿瘤学杂志

国际肿瘤学杂志 ›› 2016, Vol. 43 ›› Issue (7): 503-507.doi: 10.3760/cma.j.issn.1673422X.2016.07.006

• 论著 • 上一篇    下一篇

过氧化物酶体通路氧化应激基因与青蒿琥酯胰腺癌敏感性的相关性研究

杜冀晖, 张厚德, 魏静, 王磊, 孙廷基   

  1. 广东医学院附属南山医院中心实验室
  • 出版日期:2016-07-08 发布日期:2016-06-03
  • 基金资助:

     深圳市科技计划（201302207）

Correlation of peroxisome pathway reactive oxygen species oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer

DU  Ji-Hui, ZHANG  Hou-De, WEI  Jing, WANG  Lei, SUN  Ting-Ji   

  1. Central Laboratory, Nanshan Hospital, Guangdong Medical College, Shenzhen 518052, China
  • Online:2016-07-08 Published:2016-06-03
  • Supported by:

    Science and Technology Program of Shenzhen City (201302207)

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摘要： 目的探讨过氧化物酶体通路活性氧氧化应激关键基因的筛选及其与青蒿琥酯抗胰腺癌敏感性的相关性。方法基于美国国立癌症研究所（NCI）公共数据库55株肿瘤细胞表达谱基因芯片数据，采用Kendall相关分析方法筛选出与青蒿琥酯抗肿瘤半抑制浓度（IC50）显著相关的过氧化物酶体通路关键基因。利用荧光定量PCR验证候选基因在不同青蒿琥酯敏感性胰腺癌细胞的mRNA表达差异，并通过DAB染色检测胰腺癌细胞内过氧化物酶体含量。结果13个过氧化物酶体生物合成、增殖及其活性氧氧化应激通路关键基因mRNA表达与青蒿琥酯抗肿瘤药敏浓度IC50有显著相关性。与正常肝细胞HL7702（1.00）比较，对青蒿琥酯敏感的胰腺癌Panc1细胞过氧化物酶体生物合成基因CRAT（2.89±0.06）、PEX11B（1.90±0.07）、PEX16（1.35±0.07）mRNA相对表达水平均显著增高（t=33.00，P<0.01；t=17.85，P<0.01；t=4.54，P<0.05）；其活性氧氧化应激的抗氧化基因CAT（1.43±0.03）、SOD1（2.07±0.04）、SOD2（1.15±0.01）mRNA相对表达水平亦显著增高（t=11.71，P<0.01；t=35.85，P<0.01；t=13.22，P<0.01）；对青蒿琥酯不敏感的胰腺癌BXPC3细胞的PEX12（0.51±0.02）、CAT（0.47±0.02）、PRDX1（0.43±0.01）、SOD1（0.44±0.01）mRNA相对表达水平显著低于正常肝细胞HL7702（t=37.53，P<0.01；t=16.52，P<0.01；t=84.20，P<0.01，t=48.24，P<0.01）。DAB染色显示对青蒿琥酯敏感的胰腺癌Panc1细胞过氧化物酶体阳性表达率（61.5%）明显高于HL7702细胞（43.8%），差异有统计学意义（χ2＝16.11，P<0.01）。结论过氧化物酶体及其活性氧相关抗氧化酶CAT、PRDX1、SOD基因表达可能是影响青蒿琥酯抗胰腺癌作用敏感性的重要因素。

关键词: 胰腺肿瘤, 过氧化物酶体,  , 活性氧,  , 抗肿瘤药,  , 青蒿琥酯

Abstract: ObjectiveTo explore the screening of peroxisome pathway reactive oxygen species (ROS) oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer. MethodsBased on microarray mRNA expressions of 55 tumor cell lines in the National Cancer Institute common database, peroxisome pathwayrelated key genes which were significant correlation with halfinhibitory concentration (IC50) values of artesunate antitumor activity against human pancreatic cancer were selected by Kendall test. The candidate genes associated with artesunate sensitivity were identified and their mRNA expressions in pancreatic cancer cells were tested using fluorescent quantitative PCR. The contents of peroxidase in pancreatic cancer cells were detected through the DAB staining. ResultsThirteen key genes mRNA expressions in peroxidase pathways were significantly correlated with IC50 values for artesunate antitumor activity. Compared with normal liver cells HL7702 (1.00), CRAT (2.89±0.06), PEX11B (1.90±0.07) and PEX16 (1.35±0.07) mRNA expression levels were significantly increased in pancreatic cancer Panc1 cells which sensitive to artesunate (t=33.00, P<0.01; t=17.85, P<0.01; t=4.54, P<0.05). While CAT (1.43±0.03), SOD1 (2.07±0.04) and SOD2 (1.15±0.01) mRNA expression levels were also significantly increased in Panc1 cells which sensitive to artesunate (t=11.71, P<0.01; t=35.85, P<0.01; t=13.22, P<0.01). However, PEX12 (0.51±0.02), CAT (0.47±0.02), PRDX1 (0.43±0.01), and SOD1 (0.44±0.01) mRNA expression levels in pancreatic cancer BXPC3 cells which resistant to artesunate were significantly lower than that of HL7702 cells (t=37.53, P<0.01; t=16.52, P<0.01; t=84.20, P<0.01; t=48.24, P<0.01). DAB staining showed that the positive expression rate of peroxisomal content was apparently higher in Panc1 cells (61.5%) than that of HL7702 cells (43.8%), with a significant difference (χ2＝16.11, P<0.01). ConclusionPeroxisome and its related ROS antioxidant enzymes CAT, PRDX1, SOD gene expression may be the important factors that affect artesunate antitumor activity against human pancreatic cancer.

Key words: Pancreatic neoplasms, Peroxisomes, Reactive oxygen species, Antineoplastic agents, Artesunate