摘要
分子协同效应往往提高癌症治疗的益处。我们观察到绿茶中的主要儿茶素,( -)-表没食子儿茶素-3- 没食子酸酯酸盐(EGCG)诱导类视黄醇X受体γ(RXRγ)在SK-Ch-A1胆管细胞型肝癌细胞株和两个结肠癌细胞系株(株LoVo和多药耐药株LoVo MDR衍生物)的表达。在此基础上,我们分析了EGCG结合一个RXRγ配体——6-OH-11-O- hydroxyphenanthrene(IIF)的影响,或与视黄酸受体的配体——全反式视黄酸(RA)结合的影响。IIF单独和与EGCG结合激活视黄素x响应元件和诱导生殖细胞的核因子。相应的,EGCG单独和与IIF结合诱导67 kDa的层粘连蛋白受体的表达。我们观察到EGCG与IIF结合以较低的剂量协同生长抑制。这些效果是通过线粒体途径凋亡激活达到的。此外,LoVo细胞,我们观察到叉形头转录因子的O亚型3(FOXO3)表达的诱导,另一个分子参与细胞凋亡的激活。 最后,金属蛋白酶活性和细胞外基质金属蛋白酶诱导因子(EMMPRIN)的表达受到抑制, 用EGCG和IIF治疗后SK-CH-A1细胞的肿瘤细胞侵袭大大减少。总之,在结合使用特定的RXR配体与儿茶素可以打开胃肠道肿瘤的化学预防的新视角。
关键词: 儿茶素、胃肠道、入侵、层粘连蛋白、类视黄醇类。
Current Cancer Drug Targets
Title:Epigallocatechin-3-gallate Increases RXRγ-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines
Volume: 16 Issue: 4
Author(s): Alessio Papi, Marzia Govoni, Carmen Ciavarella, Enzo Spisni, Marina Orlandi, Fulvia Farabegoli
Affiliation:
关键词: 儿茶素、胃肠道、入侵、层粘连蛋白、类视黄醇类。
摘要: Molecules with synergistic effects often enhance the benefits of cancer therapy. We observed that the major catechin of green tea, (-)-Epigallocatechin-3-gallate (EGCG), induced retinoid X receptor-γ (RXRγ) expression in the SK-Ch-A1 cholangiocarcinoma cell line and in two colon carcinoma cell lines (LoVo and the derivative multi-drug resistant LoVoMDR). On this basis, we analyzed the effects of EGCG in combination with an RXRγ ligand, 6-OH-11-O-hydroxyphenantrene (IIF), or with a ligand of retinoic acid receptor, all-trans-retinoic acid (RA). IIF alone and in combination with EGCG activated the retinoic X response elements and induced the germ cell nuclear factor. In parallel, EGCG induced 67 kDa laminin receptor expression alone and in combination with IIF. We observed a synergistic growth inhibition with EGCG and IIF in combination at lower doses. These effects were accompanied by apoptosis activation through the mitochondrial pathway. Moreover, in LoVo cell line we observed an induction of Forkhead box O3 expression, another molecule involved in apoptosis activation. Finally, metalloproteinase activity and extracellular matrix metalloproteinase inducer (EMMPRIN) expression were inhibited and tumor cell invasion was strongly reduced in the SK-Ch-A1 cell line after treatment with EGCG and IIF. In conclusion, the use of specific RXR ligands in combination with catechins could open a new perspective in gastrointestinal tumor chemoprevention.
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Alessio Papi, Marzia Govoni, Carmen Ciavarella, Enzo Spisni, Marina Orlandi, Fulvia Farabegoli , Epigallocatechin-3-gallate Increases RXRγ-mediated Pro-apoptotic and Anti-invasive Effects in Gastrointestinal Cancer Cell Lines, Current Cancer Drug Targets 2016; 16 (4) . https://dx.doi.org/10.2174/1568009615666150817120931
DOI https://dx.doi.org/10.2174/1568009615666150817120931 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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