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豆甾醇通过调节视黄酸相关孤儿受体C来抑制肺癌进展。

Stigmasterol inhibits the progression of lung cancer by regulating retinoic acid-related orphan receptor C.

作者信息

Dong Yuan, Chen Congcong, Chen Chen, Zhang Chunxia, Zhang Lei, Zhang Yan, Li Yongliang, Dong Zhiqiang

机构信息

Department of Pharmacy, The First Affiliated Hospital of Baotou Medical College of Inner Mongolia Scientific and Technological University, Baotou City, Inner Mongolia Autonomous, China.

出版信息

Histol Histopathol. 2021 Dec;36(12):1285-1299. doi: 10.14670/HH-18-388. Epub 2021 Oct 29.

DOI:10.14670/HH-18-388
PMID:34713889
Abstract

OBJECTIVE

This study aims to investigate the role of stigmasterol in lung cancer. The study aims to investigate the role of stigmasterol in lung cancer and further explore its possible mechanisms.

METHODS

Cell Counting Kit-8 assay, 5-ethynyl-2-deoxyuridine (EdU), TUNEL and Flow cytometry were conducted to detect the proliferation and apoptosis of lung cancer cell lines. qRT-PCR and western blot were conducted to detect mRNA and protein levels of caspase-3 and caspase-9. In addition, Gene Ontology, STRING, SWISSMODEL, cellular thermal shift assay (CETSA) and Swiss Target Prediction were used to predict the targets of stigmasterol.

RESULTS

Behavioral studies showed that stigmasterol inhibited the proliferation and promoted the apoptosis of lung cancer cells. Further research revealed that retinoic acid-related orphan receptor C (RORC) directly targeted stigmasterol in lung cancer. Interestingly, rescue experiments indicated that RORC overexpression reversed the inhibitory effect of stigmasterol on lung cancer.

CONCLUSION

In our study, we confirmed the functional role of the stigmasterol-RORC axis in lung cancer progression, which provides a latent target for lung cancer treatment.

摘要

目的

本研究旨在探讨豆甾醇在肺癌中的作用。该研究旨在研究豆甾醇在肺癌中的作用,并进一步探索其可能的机制。

方法

采用细胞计数试剂盒-8法、5-乙炔基-2'-脱氧尿苷(EdU)法、TUNEL法和流式细胞术检测肺癌细胞系的增殖和凋亡。采用qRT-PCR和蛋白质印迹法检测半胱天冬酶-3和半胱天冬酶-9的mRNA和蛋白质水平。此外,利用基因本体论、STRING、SWISSMODEL、细胞热位移分析(CETSA)和瑞士靶点预测来预测豆甾醇的靶点。

结果

行为学研究表明,豆甾醇抑制肺癌细胞的增殖并促进其凋亡。进一步研究发现,维甲酸相关孤儿受体C(RORC)在肺癌中直接靶向豆甾醇。有趣的是,拯救实验表明,RORC过表达逆转了豆甾醇对肺癌的抑制作用。

结论

在我们的研究中,我们证实了豆甾醇-RORC轴在肺癌进展中的功能作用,这为肺癌治疗提供了一个潜在靶点。

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