大蒜辣素对高糖环境下肝癌细胞HepG2/mdr耐药性影响及其机制研究-东南大学学报医学版

大蒜辣素对高糖环境下肝癌细胞HepG2/mdr耐药性影响及其机制研究

单位：江苏省肿瘤医院, 江苏南京 210009

分类号：R735.7

出版年·卷·期（页码）：2015·34·第六期（987-991）

摘要：

目的:探讨大蒜辣素(allicin)对高糖环境下肝癌细胞HepG2/mdr耐药性影响及其机制. 方法:采用细胞计数试剂盒(Cell Counting Kit-8)检测细胞株HepG2/mdr活性; RT-PCR检测allicin作用后HepG2/mdr中晚期糖基化终产物受体(receptor for advanced glycation endproducts, RAGE)、核转录因子-κB(nuclear factor-kappa B,NF-κB)、多药耐药基因-1(multidrug resistance-1, MDR1) 的转录水平;蛋白质免疫印迹法(Western blotting)检测allicin作用后HepG2/mdr细胞中相关基因的蛋白表达.结果:HepG2/mdr细胞呈对数生长,可以作为后续实验的靶细胞.RT-PCR和Western blotting检测表明,随着allicin质量浓度的增加,RAGE、NF-κB、MDR1 转录水平降低,蛋白表达量减少,呈现剂量依赖性.结论:allicin能通过影响肿瘤细胞NF-κB的核转录因子活性调控下游 MDR1 基因的表达, 从而逆转高糖状态下HepG2/mdr细胞的耐药性.

Objective: To investigated mechanism of allicin on drug resistance of HepG2/mdr hepatocellular carcinoma cells in high glucose. Methods: Cell counting kit-8(CCK-8) assay was used to assess the HepG2/mdr cells activity, The expression change of mRNA and protein among RAGE、NF-κB and MDR1 were examined by RT-PCR and Western-blot. Results: The results of CCK-8 assay showed that HepG2/mdr cells present logarithmic growth could be used as target cells in the following study, RT-PCR and Western blotting experimental results showed that allicin could reduce transcription level and decrease protein expression of RAGE、NF-κB、MDR1. the phenomena were more obvious when allicin concentration increasing. Conclusion: Allicin could reverse drug resistance of tumor cells to therapy. It showed that MDR was dramatically down-regulated in a Allicin-dependent manner in response to NF-κB changes.

参考文献：

[1] 燕丹,黄培林,刘乃丰.晚期糖基化终产物对人肝癌细胞 HepG2/mdr 耐药性的影响[J].东南大学学报:医学版,2013,32(4):399-403.
[2] GAO J.Association of MDR1 gene polymorphisms with the risk of hepatocellular carcinoma in the Chinese Han population[J].Braz J Med Biol Res,2013,46(3):311-317.
[3] European Pharmacopoeia Commission.European Pharmacopoeia 6.0[M].Europe:European Directorate for the Quality of Medicines & HealthCare,2008:1961.
[4] ZHANG X C,ZHU Y,DUAN W,et al.Allicin induces apopto- sis of the MGC-803 human gastric carcinoma cell line through the p38 mitogen-activated protein kinase/caspase-3 signaling pathway[J].Mol Med Rep,2015,11(4):2755-2760.
[5] MILLEN A E,SUBAR A F,GRAUBARD B I,et al.Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial[J].Am J Clin Nutr,2007,86(6):1754-1764.
[6] KARMAKAR S,BANIK N L,PATEL S J,et al.Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells[J].Apoptosis,2007,12(4):671-684.
[7] CHUNG L Y.The antioxidant properties of garlic compounds:allyl cysteine,alliin,allicin,and allyl disulfide[J].J Med Food,2006,9(2):205-213.
[8] 燕丹,王坚,袁耀佐,等.大蒜辣素对多药耐药HepG2细胞中MDR1基因表达影响[J].时珍国医国药,2012,23(197):233-235.
[9] 中国抗癌协会肝癌专业委员会,中国抗癌协会临床肿瘤学作委员会,中华医学会肝病分会肝癌学组.原发性肝癌规范化诊治专家共识[J].临床肿瘤学杂志,2009,14(3):259-269.
[10] 沈潇,刘乃丰.可溶性晚期糖基化终产物受体基础与临床研究新进展[J].东南大学学报:医学版,2013,32(3):364-369.
[11] KAIDASHEV I P.NF-κB activation as a molecular basis of pathological process by metabolic syndrome[J].Fiziol Zh,2012,58(1):93-101.
[12] 张春勇,朱海涛,谢敏.human NF-κB miRNA干扰载体的构建[J].现在医学,2012,40(4):393-397.
[13] CHEN R F,LI Z H,KONG X H,et al.Effect of mutated IkappaBalpha transfection on multidrug resistance in hilar cholangiocarcinoma cell lines[J].World J Gastroenterol 2005,11(5):726-728.
[14] HUANG Y S,XIE N,S U Q,et al.Diallyl disulfide inhibits the proliferation of HT-29 human colon cancer cells by inducing differentially expressed genes[J].Mol Med Report,2011,4(3):553-559.
[15] AYAZ E,ALPSOY H C.Garlic (Allium sativum) and traditional medicine[J].Turkiye Parazitol Derg,2007,31(2):145-149.

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