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某物种的乙醇提取物调节胃癌MKN74细胞系中环氧合酶-2和E-钙黏蛋白的表达,并增强阿霉素的毒性。

Ethanol extracts of sp. regulate cyclooxygenase-2 and E-cadherin expression in gastric cancer MKN74 cell line and enhance doxorubicin toxicity.

作者信息

Korga Agnieszka, Ostrowska Marta, Iwan Magdalena, Skierucha Małgorzata, Józefczyk Aleksandra, Pawłowski Piotr, Dudka Jarosław, Maciejewski Ryszard, Sitarz Robert

机构信息

Department of Medical Biology, Medical University of Lublin, Lublin, Poland.

Department of Toxicology, Medical University of Lublin, Lublin, Poland.

出版信息

Food Nutr Res. 2019 Jun 25;63. doi: 10.29219/fnr.v63.3449. eCollection 2019.

Abstract

BACKGROUND

Gastric cancer (GC) remains one of the leading causes of cancer-related death. Its aetiology is multifactorial, but the major risk factor is a high in salt diet. During gastric carcinogenesis, cadherin-1 (CDH1) down-expression and cyclooxygenase 2 (COX2) overexpression may be observed. The intensity of these alterations contributes to the GC invasion, its metastases and poor prognosis. As the diet plays a significant role in the aetiology of GC, it is reasonable to include the nutritional chemoprevention agents. One of the plant genus demonstrating chemoprotective properties is genus, which includes garlic. The relationship between CDH1 and COX2 in GC cells treated with species extract has never been evaluated.

METHODS

In this study, the MKN28 and MKN74 GC cell lines were treated with ethanol extracts of L., Lam., L. (from Malaysia and Poland), Rendle and L. The cytotoxicity of the extracts and their influence on COX2 and CDH1 mRNA and protein expression were evaluated as well as their influence on doxorubicin's (DOX) efficacy - a drug that has been used in GC treatment.

RESULTS

Among the tested species, ethanol extracts of L. (Poland and Malaysia), Rendle and L. influenced the levels of CDH1 and COX2, but only in the MKN74 cell line. Thus, it is possible that tumours with increased COX2 expression will be more susceptible to garlic treatment. Observed phenomenon was independent of extract's toxicity. In comparison to DOX, tested extracts were more toxic. Moreover, revealed synergistic effect with the drug.

CONCLUSION

In conclusion, the results indicate the potential application of genus to GC chemoprevention and treatment support through CDH restoration and COX2 downregulation. This issue needs further investigations as it might be used in clinics.

摘要

背景

胃癌(GC)仍然是癌症相关死亡的主要原因之一。其病因是多因素的,但主要危险因素是高盐饮食。在胃癌发生过程中,可观察到钙黏蛋白-1(CDH1)表达下调和环氧合酶2(COX2)表达上调。这些改变的强度有助于胃癌的侵袭、转移及不良预后。由于饮食在胃癌病因中起重要作用,纳入营养化学预防剂是合理的。具有化学保护特性的植物属之一是大蒜属。从未评估过用大蒜属植物提取物处理的GC细胞中CDH1和COX2之间的关系。

方法

在本研究中,用大蒜、洋葱、韭菜(来自马来西亚和波兰)、山蒜和薤白的乙醇提取物处理MKN28和MKN74 GC细胞系。评估提取物的细胞毒性及其对COX2和CDH1 mRNA及蛋白表达的影响,以及它们对阿霉素(DOX)疗效的影响——DOX是一种已用于GC治疗的药物。

结果

在测试的物种中,大蒜(波兰和马来西亚)、山蒜和薤白的乙醇提取物影响了CDH1和COX2的水平,但仅在MKN74细胞系中。因此,COX2表达增加的肿瘤可能对大蒜治疗更敏感。观察到的现象与提取物的毒性无关。与DOX相比,测试提取物毒性更大。此外,提取物与该药物显示出协同作用。

结论

总之,结果表明大蒜属植物通过恢复CDH和下调COX2在GC化学预防和治疗支持方面的潜在应用。由于其可能用于临床,这个问题需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24c4/6604903/6d80be8afb2b/FNR-63-3449-g001.jpg

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