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二烯丙基硫醚、二烯丙基二硫醚和二烯丙基三硫醚在体外和体内影响colo 205 人结肠癌细胞耐药基因的表达。

Diallyl sulfide, diallyl disulfide and diallyl trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo.

机构信息

Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan.

出版信息

Phytomedicine. 2012 May 15;19(7):625-30. doi: 10.1016/j.phymed.2012.02.004. Epub 2012 Mar 5.

Abstract

To elevate chemo-resistance of human cancer cells is a major obstacle in the treatment and management of malignant cancers. Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are presented in the Alliaceae family particularly in garlic. Although DAS, DADS and DATS have been shown to exhibit anticancer activities, there is little information on effects of these compounds on drug resistant genes in human colon cancer cells in vitro and in vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 μM for 24-h and 48-h incubations promoted expression of drug resistant genes in colo 205 human colon cancer cells. In vitro experiments indicated that DATS promoted gene expression of multidrug resistant 1 (Mdr1) (p<0.05), and DAS and DADS promoted MRP3 gene expression and DATS alone stimulated gene expression of multidrug resistance-associated protein-1 (MRP1) (p<0.05) in colo 205 cells. In vivo studies demonstrated that DADS and DATS induced Mdr1 and MRP1 gene expression (p<0.05). DADS promoted MRP3 gene expression (p<0.05) as well as DADS and DATS increased MRP4 and MRP6 gene expression (p<0.05) in the colo 205 xenograft mice. Based on our in vitro and in vivo results, diallyl polysulfides (DAS, DADS and DATS) affected the gene expression of the multidrug resistance in colo 205 human colon cancer cells in vitro and in vivo.

摘要

提高人类癌细胞的化疗耐药性是恶性癌症治疗和管理的主要障碍。二烯丙基硫醚(DAS)、二烯丙基二硫醚(DADS)和二烯丙基三硫醚(DATS)存在于葱属植物中,特别是大蒜中。虽然已经证明 DAS、DADS 和 DATS 具有抗癌活性,但关于这些化合物对体外和体内人结肠癌耐药基因的影响的信息很少。在此,我们首次表明,DAS、DADS 和 DATS 在 25 μM 孵育 24 小时和 48 小时可促进 colo 205 人结肠癌细胞中耐药基因的表达。体外实验表明,DATS 促进多药耐药基因 1(Mdr1)的基因表达(p<0.05),DAS 和 DADS 促进多药耐药相关蛋白 3(MRP3)基因表达,而 DATS 单独刺激多药耐药相关蛋白 1(MRP1)的基因表达(p<0.05)colo 205 细胞。体内研究表明,DADS 和 DATS 诱导 Mdr1 和 MRP1 基因表达(p<0.05)。DADS 促进 MRP3 基因表达(p<0.05)以及 DADS 和 DATS 增加 MRP4 和 MRP6 基因表达(p<0.05)在 colo 205 异种移植小鼠中。基于我们的体外和体内结果,二烯丙基多硫化物(DAS、DADS 和 DATS)影响了 colo 205 人结肠癌细胞的体外和体内多药耐药基因的表达。

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