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蜂毒和蜂肽通过上调 BRMS1 和 DRG1 基因对乳腺癌细胞的抗转移作用。

Anti-metastatic Effects of Bee Venom and Melittin in Breast Cancer Cells by Upregulation of BRMS1 and DRG1 Genes.

机构信息

Department of Molecular Biology and Genetics, Karadeniz Technical University, Trabzon, Turkey.

Department of Biochemistry, Faculty of Science, Karadeniz Technical University, Trabzon, Turkey.

出版信息

Chem Biol Drug Des. 2024 Oct;104(4):e14637. doi: 10.1111/cbdd.14637.

DOI:10.1111/cbdd.14637
PMID:39396919
Abstract

Apitherapy has started to gain tremendous recognition because of extraordinary pharmacological importance of honeybee-related ingredients and their derivatives. There has been a renewed interest in the bee venom-based therapies. Interdisciplinary researchers are studying the chemistry and translational value of venom for effective cancer treatment. Bee venom and its major component, melittin, are cytotoxic in cancer cells. In this study, MTT and scratch assays were performed for analysis of melittin-mediated antimetastatic effects. QPCR was used for expression profiling of metastasis-related genes. Three anti-metastatic genes (BRMS1, DRG1, and KAI1/CD82) were studied for the first time after bee venom and melittin treatment in MDA-MB-231 breast cancer cells compared with normal breast cells, and two prometastatic genes (EGFR and WNT7B) were also examined. KAI1/CD82 and BRMS1 are the negative regulators of EGFR. WNT7B is a negative regulator of KAI1/CD82. Selective cytotoxicity of bee venom and melittin was found to be higher as compared to cisplatin. Melittin induced an increase in the expression of BRMS1 and DRG1, whereas bee venom upregulated DRG1 and KAI1/CD82 expression in breast cancer. WNT7B was downregulated in bee venom-treated breast cancer cells. Results suggested that bee venom/melittin exerted antimetastatic effects primarily through upregulation of BRMS1, DRG1, and KAI1/CD82, and downregulation of WNT7B.

摘要

蜂疗法因其与蜜蜂相关的成分及其衍生物的非凡药理重要性而开始获得巨大认可。人们对基于蜂毒液的疗法重新产生了兴趣。跨学科研究人员正在研究毒液的化学和转化价值,以实现有效的癌症治疗。蜂毒液及其主要成分蜂肽在癌细胞中具有细胞毒性。在这项研究中,进行了 MTT 和划痕实验以分析蜂肽介导的抗转移作用。使用 QPCR 进行与转移相关的基因表达谱分析。首次在 MDA-MB-231 乳腺癌细胞中研究了三种抗转移基因(BRMS1、DRG1 和 KAI1/CD82),与正常乳腺细胞相比,在蜂毒液和蜂肽处理后研究了三种抗转移基因(BRMS1、DRG1 和 KAI1/CD82),并且还研究了两种促转移基因(EGFR 和 WNT7B)。KAI1/CD82 和 BRMS1 是 EGFR 的负调节剂。WNT7B 是 KAI1/CD82 的负调节剂。与顺铂相比,发现蜂毒和蜂肽的选择性细胞毒性更高。蜂肽诱导 BRMS1 和 DRG1 的表达增加,而蜂毒液上调乳腺癌中 DRG1 和 KAI1/CD82 的表达。WNT7B 在蜂毒液处理的乳腺癌细胞中下调。结果表明,蜂毒/蜂肽主要通过上调 BRMS1、DRG1 和 KAI1/CD82 以及下调 WNT7B 发挥抗转移作用。

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