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通过生物信息学分析和验证确定熊果酸对视网膜母细胞瘤细胞的抗癌活性。

Anticancer activity of ursolic acid on retinoblastoma cells determined by bioinformatics analysis and validation.

作者信息

Zhou Dan, Bao Qi, Fu Songbin

机构信息

Department of Ophthalmology, Suzhou High Tech Zone People's Hospital, Suzhou, China.

Department of Ophthalmology, Harbin Medical University, Harbin, China.

出版信息

Ann Transl Med. 2021 Oct;9(20):1548. doi: 10.21037/atm-21-4617.

Abstract

BACKGROUND

This article aims to explore whether ursolic acid (UA) inhibits the progression of retinoblastoma (Rb) by regulating stearoyl-CoA desaturase (SCD).

METHODS

The Gene Expression Omnibus (GEO) database was used to filter the chip, then the GEO2R software was used to analyze the microarray data (GSE97508, GSE24673, and GSE110811). Gene set enrichment analysis (GSEA) was used to analyze the relationship between the expression level of SCD and the proliferation, migration, invasion, and inflammation in Rb patients. SO-RB50 and Y79 cell proliferation, migration, and invasion were assessed by the CCK-8 assay, the colony formation assay, the Transwell assay, and the wound scratch test. The protein expression levels of SCD were measured by western blot. The mRNA expression levels of IL-8, IL-6, CXCL1, and CCL2 were measured by RT-qPCR. The protein expression levels of IL-8 and IL-6 were measured by ELISA. A xenograft nude mouse model was established to evaluate the effect of UA on tumor growth in male BALB/c mice.

RESULTS

The expression levels of SCD were related to cell proliferation, migration, invasion, and inflammation. UA inhibited SO-RB50 and Y79 cell proliferation, migration, and invasion. At the same time, UA suppressed tumor growth in the xenograft nude mouse model. Overexpression of SCD promoted SO-RB50 and Y79 cell proliferation, migration, invasion, and inflammation, while SCD knockout inhibited SO-RB50 and Y79 cell proliferation, migration, invasion, and inflammation. Importantly, UA inhibited the proliferation, migration, and invasion of Rb cells through SCD inhibition.

CONCLUSIONS

UA inhibited the proliferation, migration, and invasion of Rb cells through SCD. This provides a new scientific basis for targeted therapy of Rb.

摘要

背景

本文旨在探讨熊果酸(UA)是否通过调节硬脂酰辅酶A去饱和酶(SCD)来抑制视网膜母细胞瘤(Rb)的进展。

方法

利用基因表达综合数据库(GEO)筛选芯片,然后使用GEO2R软件分析微阵列数据(GSE97508、GSE24673和GSE110811)。基因集富集分析(GSEA)用于分析SCD表达水平与Rb患者增殖、迁移、侵袭和炎症之间的关系。通过CCK-8检测、集落形成检测、Transwell检测和划痕试验评估SO-RB50和Y79细胞的增殖、迁移和侵袭。通过蛋白质免疫印迹法检测SCD的蛋白表达水平。通过逆转录定量聚合酶链反应(RT-qPCR)检测白细胞介素8(IL-8)、白细胞介素6(IL-6)、CXC趋化因子配体1(CXCL1)和C-C基序趋化因子配体2(CCL2)的mRNA表达水平。通过酶联免疫吸附测定(ELISA)检测IL-8和IL-6的蛋白表达水平。建立异种移植裸鼠模型以评估UA对雄性BALB/c小鼠肿瘤生长的影响。

结果

SCD的表达水平与细胞增殖、迁移、侵袭和炎症相关。UA抑制SO-RB50和Y79细胞的增殖、迁移和侵袭。同时,UA抑制异种移植裸鼠模型中的肿瘤生长。SCD过表达促进SO-RB50和Y79细胞的增殖、迁移、侵袭和炎症,而SCD基因敲除则抑制SO-RB50和Y79细胞的增殖、迁移,侵袭和炎症。重要的是,UA通过抑制SCD来抑制Rb细胞的增殖、迁移和侵袭。

结论

UA通过SCD抑制Rb细胞的增殖、迁移和侵袭。这为Rb的靶向治疗提供了新的科学依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33c8/8576664/79674b6aa687/atm-09-20-1548-f1.jpg

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