水飞蓟素对肝细胞癌细胞系（HepG2）中微-RNA-21、基质金属蛋白酶（MMP）2 和 9 以及基质金属蛋白酶组织抑制剂（TIMP）1 和 2 表达的影响

Q2 Medicine Medical Journal of the Islamic Republic of Iran Pub Date : 2024-07-09 eCollection Date: 2024-01-01 DOI:10.47176/mjiri.38.78

Maryam Hormozi, Meysam Moulaee, Mahdi Alaee, Nasim Beigi Boroujeni, Mandana Beigi Boroujeni

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摘要

背景：水飞蓟素是一种黄酮木脂素，具有保护肝脏、抗氧化、抗炎、抗癌和保护心脏等多种药用特性。本研究旨在探讨水飞蓟素对肝癌 HepG2 细胞系中 mir-21、基质金属蛋白酶（MMP）及其组织抑制剂（TIMPs）表达水平的影响：对伊朗德黑兰巴斯德研究所制备的人 HepG2 细胞进行了体外实验研究。根据 MTT 检测法，将 0（对照组）、50、100 和 150 µM 四种浓度的水飞蓟素作为研究组。基因表达研究采用实时 PCR 技术进行。研究基因包括 mir-21、MMP-2、MMP-9、TIMP-1 和 TIMP-2。此外，还研究了一些与细胞凋亡相关的基因，包括 BAX、BCL2 和 Caspase3 (CAS3)。GAPDH 用作内部对照。在显著性水平为 0.05 的情况下，用 REST 程序对表达量的对数进行 t 检验，计算相对表达量：在剂量为 100 µM 和 150 µM 时，TIMP 基因以及凋亡激活基因 CAS3 和 BAX 的表达明显上调（P < 0.05）。明显下调的基因包括所有浓度下的 MMP-9、100 µM 浓度下的 MMP-2，以及 50 µM 和 100 µM 浓度下的凋亡抑制基因 BCL2（P < 0.05）。此外，mir-21 作为一种致癌微 RNA，在所有剂量下均出现显著下调（P < 0.05）。所有结果均与对照组进行了比较：本研究表明，水飞蓟素可通过增加细胞凋亡和改变 MMP-2、MMP-9、TIMP-1、TIMP-2 和 mir-21 的表达，在基因表达水平上影响 HepG2 细胞系。这些发现相互吻合，有利于抑制该细胞株的肿瘤活性。

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Background: Silymarin is a flavonolignan that has various medicinal properties such as liver protection, antioxidant, anti-inflammatory, anti-cancer and heart protection activities. The aim of this study was to investigate the effect of silymarin on the expression level of mir-21, matrix metalloproteinase(MMP), and their tissue inhibitors (TIMPs) in liver cancer HepG2 cell line.

Methods: An in-vitro experimental study was conducted on the human HepG2 cells prepared from Pasteur Institute, Tehran, Iran. Four concentrations of 0 (control), 50, 100, and 150 µM of silymarin were considered as the study groups according to the MTT assay. Gene expression study was performed using real-time PCR. The studied genes were mir-21, MMP-2, MMP-9, TIMP-1 and TIMP-2. In addition, some apoptosis-related genes including BAX, BCL2 and Caspase3 (CAS3) were investigated. GAPDH was used as an internal control. Relative expression was calculated by REST program using t-test on the logarithm of expression considering a significance level of 0.05.

Results: The significant up-regulations consisted of TIMP genes for doses 100 µM and 150 µM, and the apoptosis activating genes CAS3 and BAX (P < 0.05). The significant down-regulations consisted of MMP-9 in all concentrations, MMP-2 in concentration 100 µM, and the apoptosis inhibitory gene BCL2 in concentrations 50 µM and 100 µM (P < 0.05). In addition, mir-21 as an oncogenic micro-RNA showed significant down-regulation for all doses (P < 0.05). All the comparisons were with the control group.

Conclusion: The present study showed that silymarin could affect the HepG2 cell line at the gene expression level via increasing apoptosis and changing the expression of MMP-2, MMP-9, TIMP-1, TIMP-2 and mir-21. These findings were in line with each other and in favor of suppression of tumoral activity in this cell line.

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