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迷迭香酸和阿霉素作用后OVCAR3细胞中FOXP3基因表达的调控

Modulation of FOXP3 Gene Expression in OVCAR3 Cells Following Rosmarinic Acid and Doxorubicin Exposure.

作者信息

Toprak Veysel, Özdemir İlhan, Öztürk Şamil, Yanar Orhan, Kizildemir Yusuf Ziya, Tuncer Mehmet Cudi

机构信息

Private Metrolife Hospital, Şanlıurfa 63320, Turkey.

Department of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum 25070, Turkey.

出版信息

Pharmaceuticals (Basel). 2024 Nov 28;17(12):1606. doi: 10.3390/ph17121606.

Abstract

Ovarian cancer has the highest mortality rate in the world. Treatment methods are listed as surgery, chemotherapy, and radiotherapy, depending on the stage of cancer, but developing resistance to chemotherapy increases the need for alternative agents that act on the same pathways. The effects of rosmarinic acid (RA) and doxorubicin (DX) on the activation of FOXP3, an important tumor suppressor gene, in OVCAR3 cells were examined. In this study, a human ovarian adenocarcinoma cell line was used. MTT analysis was performed to reveal the result of RA and DX on ovarian cancer cell proliferation. Expression levels of FOXP3 for cell proliferation and Capase-3 for apoptosis were determined by RT-qPCR. The wound healing model was applied to determine cell migration rates. The results were evaluated with one-way ANOVA in an SPSS 20.0 program as ≤ 0.05. It was determined that RA and DX alone and in combination inhibited the proliferation of OVCAR3 cells in different doses for 24, 48, and 72 h, and caused the cells to die by causing them to undergo apoptosis. Caspase-3 expression increased approximately tenfold in OVCAR3 cells, while FOXP3 expression was upregulated only in RA treatment and was downregulated in DX and RA + DX treatments. According to the results of our study, it was determined that the FOXP3 signaling pathway related to apoptosis, and proliferation was affected by the combination treatment of RA and DX in the OVCAR3 cancer cell line. This shows that RA will gain an important place in cancer treatment with more comprehensive study.

摘要

卵巢癌是全球死亡率最高的癌症。根据癌症分期,治疗方法包括手术、化疗和放疗,但对化疗产生耐药性增加了对作用于相同途径的替代药物的需求。本研究检测了迷迭香酸(RA)和阿霉素(DX)对卵巢癌细胞系OVCAR3中重要肿瘤抑制基因FOXP3激活的影响。本研究使用了一种人卵巢腺癌细胞系。采用MTT分析法揭示RA和DX对卵巢癌细胞增殖的影响。通过RT-qPCR测定细胞增殖相关的FOXP3和凋亡相关的Caspase-3的表达水平。应用伤口愈合模型测定细胞迁移率。结果在SPSS 20.0程序中采用单因素方差分析进行评估,P≤0.05。结果表明,RA和DX单独及联合使用在不同剂量下对OVCAR3细胞增殖有抑制作用,作用24、48和72小时后可诱导细胞凋亡。Caspase-3在OVCAR3细胞中的表达增加了约10倍,而FOXP3仅在RA处理时上调,在DX及RA+DX处理时下调。根据本研究结果,确定在OVCAR3癌细胞系中,与凋亡和增殖相关的FOXP3信号通路受RA和DX联合治疗的影响。这表明,随着更全面的研究,RA在癌症治疗中将占据重要地位。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d351/11676701/707c8bbd2b31/pharmaceuticals-17-01606-g001.jpg

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