消化道肿瘤药物相关基因单核苷酸多态性分析

刘颖, 马旭, 吴海伟, 张艳华

中国药学杂志 ›› 2016, Vol. 51 ›› Issue (24) : 2124-2128.

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中国药学杂志 ›› 2016, Vol. 51 ›› Issue (24) : 2124-2128. DOI: 10.11669/cpj.2016.24.011
消化道肿瘤药物的研发与临床应用专栏

消化道肿瘤药物相关基因单核苷酸多态性分析

  • 刘颖, 马旭, 吴海伟, 张艳华*
作者信息 +

Single Nucleotide Polymorphisms Analysis of Drug Related Genes in Digestive Tract Cancer

  • LIU Ying, MA Xu, WU Hai-wei, ZHANG Yan-hua*
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文章历史 +

摘要

目的 探讨化疗耐药与肿瘤干细胞的关系以及逆转化疗耐药的途径,指导抗肿瘤合理用药。方法 分别培养普通型和耐药型肝癌细胞系HepG-2,建立细胞增殖模型观察化疗药物氟尿嘧啶和干细胞诱导分化剂全反式维甲酸对肝癌细胞的增殖抑制作用,通过流式分析术比较普通型和耐药型HepG-2细胞中肿瘤干细胞的含量差异,运用Western Blot和Realtime-PCR技术检测普通型和耐药型肝癌细胞中干性基因的表达水平。结果 氟尿嘧啶单用时,其对耐药型HepG-2细胞的增殖抑制作用明显低于普通型细胞;加入全反式维甲酸后,耐药型细胞的增殖速率显著降低。与普通型HepG-2细胞相比,耐药型细胞中CD44和CD326阳性细胞的比例明显增高,ABCG2、BMI、OCT4的mRNA和蛋白表达量均显著升高;而加入维甲酸后,ABCG2、BMI、OCT4蛋白表达水平又有不同程度的下降。结论 化疗耐药与肿瘤干细胞的富集相关,维甲酸可以下调肿瘤干细胞相关基因的表达、逆转肿瘤细胞的耐药性。这为临床上合理应用抗肿瘤药物提供了新的思路。

Abstract

OBJECTIVE To analyze of the characteristics of single nucleotide polymorphisms of the commonantineoplastics in the treatment of gastric cancer and colorectal cancer in our hospital. METHODS Venous blood was collected from patients with digestive tract tumor, and the drug related gene loci were detected by fluorescence staining in situ hybridization. The original data are stored in Microsoft Excel to establish a database for routine statistics and chi square test was conducted to determine whether the distribution of allele frequency distribution is in accordance with the law of Hardy Weinberg. RESULTS A Total of 1 743 loci of 14 drug related genes were detected in 242 patients. The loci genotype distribution were in accordance with Hardy Weinberg equilibrium except dihydrotestosterone dihydropyrimidine dehydrogenase gene (DPYD), methylenetetrahydrofolate reductase gene (MTHFR) and cytochrome P4501B1 gene (CYP1B1). CONCLUSION The patients with digestive tract tumor in China have their own characteristics in single nucleotide polymorphisms of drug related genes. We should take this as the basis for accurate anti-tumor drug treatment.

关键词

消化道肿瘤 / 药物基因组学 / 单核苷酸多态性

Key words

gastrointestinal neoplasm / pharmacogenomics / single nucleotide polymorphism

引用本文

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刘颖, 马旭, 吴海伟, 张艳华. 消化道肿瘤药物相关基因单核苷酸多态性分析[J]. 中国药学杂志, 2016, 51(24): 2124-2128 https://doi.org/10.11669/cpj.2016.24.011
LIU Ying, MA Xu, WU Hai-wei, ZHANG Yan-hua. Single Nucleotide Polymorphisms Analysis of Drug Related Genes in Digestive Tract Cancer[J]. Chinese Pharmaceutical Journal, 2016, 51(24): 2124-2128 https://doi.org/10.11669/cpj.2016.24.011
中图分类号: R973   

参考文献

[1] RODRíGUEZ-VICENTE A E, LUMBRERAS E, HERNNDEZ J M, et al. Pharmacogenetics and pharmacogenomics as tools in cancer therapy[J]. Drug Metab Person Ther, 2016, 31(1):25-34.
[2] CAUDLE K E, THORN C F, KLEIN T E, et al. Clinical pharmacogenetics implementation consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing[J]. Clin Pharmacol Ther, 2013, 94(6):640-645.
[3] YANG M D, SHI W L, ZHAI S D. Genotype frequencies of DPYD*2A in healthy populations: a synthetic analysis[J]. Chin J Clin Pharmacol(中国临床药理学杂志), 2016, 32(10):936-940.
[4] LUNENBURG C A, VAN STAVEREN M C, GELDERBLOM H, et al. Evaluation of clinical implementation of prospective DPYD genotyping in 5-fluorouracil- or capecitabine-treated patients[J]. Pharmacogenomics, 2016, 17(7):721-729.
[5] CORTEJOSO L, GARCíA-GONZLEZ X, GARCíA M I, et al. Cost-effectiveness of screening for DPYD polymorphisms to prevent neutropenia in cancer patients treated with fluoropyrimidines[J]. Pharmacogenomics, 2016, 17(9):979-984.
[6] ZHENG Y,YIN J Y,ZHOU H H,et al. Advancesinrelationship of genetic polymorphism with the toxicity caused by platinum- based therapy [J]. Chin J Clin Pharmacol Thera(中国临床药理学与治疗学),2014,19(9):1051-1056.
[7] MOYER A M, SALAVAGGIONE O E, WU T Y, et al. Glutathione S-transferase P1:gene sequence variation and functional genomic studies[J]. Cancer Res, 2008, 68(12): 4791-4801.
[8] CHEN Y X, LI X M, WEN F Q, et al. Effect of GSTP1 genetic polymorphisim on sensitivity of platimum-based chemotherapy[J]. Chin J Clin Oncol(中国肿瘤临床), 2011, 38(17):999-1001.
[9] BARBARINOA J M, HAIDARC C E, KLEINA T E, et al. PharmGKB summary: very important pharmacogene information for UGT1A1[J]. Pharmacogenet Genomics, 2014, 24(3):177-183.
[10] GUO D,PANG L F,ZHOU H H,Progress in the pharmacogenomics of UDP-glucuronosyltransferase[J].Chin J New Drugs(中国新药杂志),2011,20(13):1188-1191.
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