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胸腺醌与阿霉素对人卵巢腺癌细胞系OVCAR3中EGFR/FOXP3信号通路影响的研究

Investigation of the effect of thymoquinone and doxorubicin on the EGFR/FOXP3 signaling pathway in OVCAR3 human ovarian adenocarcinoma cells.

作者信息

Özdemir İlhan, Aktaş Ayfer Şanli, Tuncer Mehmet Cudi

机构信息

Atatürk University - Faculty of Medicine - Department of Gynecology and Obstetrics - Erzurum - Turkey.

Dicle University - Faculty of Medicine - Department of Histology and Embryology - Diyarbakir - Turkey.

出版信息

Acta Cir Bras. 2025 Mar 31;40:e401725. doi: 10.1590/acb401725. eCollection 2025.

DOI:10.1590/acb401725
PMID:40172364
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11960576/
Abstract

PURPOSE

To investigate the cytotoxic and apoptotic effects of the combination of doxorubicin (Dox) and thymoquinone (TQ) on ovarian adenocarcinoma cells (OVCAR3) via the EGFR/FOXP3 signaling pathway.

METHODS

We used human OVCAR3 and human skin keratinocyte cells (HaCaT). Different concentrations of TQ and Dox were applied to the cells for 24, 48, and 72 hours, and the cytotoxicity level was determined via the MTT method. Expression levels of EGFR/FOXP3 for cell proliferation and apoptosis were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot analysis. The colony counting was performed after DAPI staining, and the effect on cell proliferation was determined.

RESULTS

Cytotoxicity was found to be highest with TQ and Dox treatments, and cell migration was prevented, especially in the group that received combined TQ and Dox treatment. Moreover, using RT-qPCR analysis, activity in the EGFR and FOXP3 pathway was found to be downregulated the most with TQ, and the amount of protein decreased with TQ and Dox.

CONCLUSIONS

The findings showed that the greatest cytotoxic effect and the most apoptosis occurred during TQ treatment. Additionally, it was determined that a significant decrease in EGFR and FOXP3 levels occurred with the application of TQ and Dox.

摘要

目的

通过表皮生长因子受体/叉头框蛋白3（EGFR/FOXP3）信号通路研究阿霉素（Dox）和百里醌（TQ）联合应用对卵巢腺癌细胞（OVCAR3）的细胞毒性和凋亡作用。

方法

我们使用了人OVCAR3细胞和人皮肤角质形成细胞（HaCaT）。将不同浓度的TQ和Dox作用于细胞24、48和72小时，通过MTT法测定细胞毒性水平。通过定量逆转录聚合酶链反应（RT-qPCR）和蛋白质免疫印迹分析确定细胞增殖和凋亡相关的EGFR/FOXP3表达水平。在4',6-二脒基-2-苯基吲哚（DAPI）染色后进行集落计数，确定对细胞增殖的影响。

结果

发现TQ和Dox处理的细胞毒性最高，细胞迁移受到抑制，尤其是在接受TQ和Dox联合处理的组中。此外，使用RT-qPCR分析发现，TQ对EGFR和FOXP3通路的活性下调最为明显，且TQ和Dox处理后蛋白质含量降低。

结论

研究结果表明，TQ处理期间细胞毒性作用最强，凋亡现象最明显。此外，确定TQ和Dox联合应用后EGFR和FOXP3水平显著降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/81228f6fc55c/1678-2674-acb-40-e401725-gf10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/1bf11647010e/1678-2674-acb-40-e401725-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/857d0f425f98/1678-2674-acb-40-e401725-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/d971df5d2ed5/1678-2674-acb-40-e401725-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/abdbe35b73c6/1678-2674-acb-40-e401725-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/a9c31954ac9a/1678-2674-acb-40-e401725-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/e674b0f6ed98/1678-2674-acb-40-e401725-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/d6376648a0c5/1678-2674-acb-40-e401725-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/2d10ea545b65/1678-2674-acb-40-e401725-gf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/e6e4518130d1/1678-2674-acb-40-e401725-gf09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/81228f6fc55c/1678-2674-acb-40-e401725-gf10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/1bf11647010e/1678-2674-acb-40-e401725-gf01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/857d0f425f98/1678-2674-acb-40-e401725-gf02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/d971df5d2ed5/1678-2674-acb-40-e401725-gf03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/abdbe35b73c6/1678-2674-acb-40-e401725-gf04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/a9c31954ac9a/1678-2674-acb-40-e401725-gf05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/e674b0f6ed98/1678-2674-acb-40-e401725-gf06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/d6376648a0c5/1678-2674-acb-40-e401725-gf07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/2d10ea545b65/1678-2674-acb-40-e401725-gf08.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/e6e4518130d1/1678-2674-acb-40-e401725-gf09.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261e/11960576/81228f6fc55c/1678-2674-acb-40-e401725-gf10.jpg

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