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卡他任治疗对HepG2细胞中miRNA34和miRNA29水平的影响及其与Bcl-2和Nrf2表达水平的关联。

Impact of cataranthine treatment on miRNA34 and miRNA29 levels in HepG2 cells and their association with the expression levels of Bcl-2 and Nrf2.

作者信息

Heidari-Kalvani Nafiseh, Mehdikhani Fariba, Mohammadi Yaser, Barjesteh Fereshteh, Bahreini Elham

机构信息

Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Mol Biol Rep. 2024 Dec 29;52(1):88. doi: 10.1007/s11033-024-10176-6.

Abstract

INTRODUCTION

Cataranthine is an alkaloid used in the development of anti-cancer drugs. In this study, the effect of cataranthine is assessed by measuring the levels of miR-34 and miRNA-29, which are effective regulators of BCL-2 and NRF-2 gene expression, and their relation to the survival of HCC cells.

METHODS

This study used cataranthine, and the HepG2 cell line. The MTT test was used to determine the appropriate concentration of cataranthine for treatment (IC50). Oxidative stress status was assessed by evaluating TAC (total antioxidant capacity), TOS (total oxidant status), and MAD (malondialdehyde) levels. Flow cytometry was used to investigate apoptosis. The expression levels of Nrf2, Bcl2, miRNA34, and miRNA29 genes in HepG2 were evaluated by RT-PCR.

RESULTS

We observed that cataranthine significantly reduced the levels of oxidative markers (MAD, and TOS) and, conversely, increased the level of antioxidant markers in HepG2 cells. Treatment of HepG2 cells with different doses of cataranthine significantly increased the expression of Nrf2 and Bcl-2 genes, while significantly decreasing the expression of miR29 and miR34 genes.

CONCLUSION

These findings suggest that cataranthine may exert its anticancer effects by reducing oxidative stress and promoting apoptosis, while decrease in miR34 and miR29 as well as increase in Nrf2 and Bcl2 may act as resistance mechanisms in cancer cells. The results highlight the dual potential of cataranthine in regulating cellular responses to oxidative stress and cell death in liver cancer, with dose-dependent modulatory effects.

摘要

引言

长春花宁是一种用于抗癌药物研发的生物碱。在本研究中,通过测量miR - 34和miRNA - 29的水平来评估长春花宁的作用,它们是BCL - 2和NRF - 2基因表达的有效调节因子,并且研究它们与肝癌细胞存活的关系。

方法

本研究使用了长春花宁和HepG2细胞系。采用MTT试验确定长春花宁治疗的合适浓度(IC50)。通过评估总抗氧化能力(TAC)、总氧化状态(TOS)和丙二醛(MAD)水平来评估氧化应激状态。使用流式细胞术研究细胞凋亡。通过RT - PCR评估HepG2中Nrf2、Bcl2、miRNA34和miRNA29基因的表达水平。

结果

我们观察到长春花宁可显著降低HepG2细胞中氧化标志物(MAD和TOS)的水平,相反,可提高抗氧化标志物的水平。用不同剂量的长春花宁处理HepG2细胞可显著增加Nrf2和Bcl - 2基因的表达,同时显著降低miR29和miR34基因的表达。

结论

这些发现表明,长春花宁可能通过降低氧化应激和促进细胞凋亡发挥其抗癌作用,而miR34和miR29的降低以及Nrf2和Bcl2的增加可能作为癌细胞的耐药机制。结果突出了长春花宁在调节肝癌细胞对氧化应激和细胞死亡的细胞反应方面的双重潜力,具有剂量依赖性调节作用。

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