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氧化苦参碱通过抑制β-连环蛋白表达抑制肾细胞癌进展。

Oxymatrine Inhibits Renal Cell Carcinoma Progression by Suppressing β-Catenin Expression.

作者信息

Jin Yinshan, Liu Jiannan, Liu Yadong, Liu Yang, Guo Guiying, Yu Shiliang, An Ruihua

机构信息

Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Pharmacol. 2020 Jun 5;11:808. doi: 10.3389/fphar.2020.00808. eCollection 2020.

Abstract

AIMS

Oxymatrine (OMT) has been identified to possess immunomodulatory, antiinflammatory and anticancer properties. This study aimed to investigate its precise function and the underlying molecular mechanisms in renal cell carcinoma progression.

METHODS

The antineoplastic effect of oxymatrine was investigated by CCK-8 assay, cell cycle analysis, apoptosis assay, wound healing experiment, transwell assay, and drug-sensitivity analysis in renal cancer cells following oxymatrine treatment. The modulation of oxymatrine on β-catenin was analyzed through western blot and immunofluorescence assay. β-catenin overexpression was employed to determine the key role of β-catenin in oxymatrine-inhibited renal cell carcinoma . In addition, animal model was established to investigate the effect of oxymatrine on tumor growth .

RESULTS

Oxymatrine inhibited renal cell carcinoma progression , including cell proliferation, apoptosis, migration, invasion and chemotherapy sensitivity. Further mechanistic studies demonstrated that oxymatrine exerted its antineoplastic effect through suppressing the expression of β-catenin. Moreover, in nude mice model, oxymatrine exhibited remarkable inhibition of tumor growth, which was consistent with our results.

CONCLUSIONS

Our findings illuminate oxymatrine as an effective antitumor agent in renal cell carcinoma, and suggest it a promising therapeutic application in renal cell carcinoma treatment.

摘要

目的

氧化苦参碱(OMT)已被证实具有免疫调节、抗炎和抗癌特性。本研究旨在探讨其在肾细胞癌进展中的具体作用及潜在分子机制。

方法

通过CCK-8法、细胞周期分析、凋亡检测、伤口愈合实验、Transwell实验及氧化苦参碱处理后肾癌细胞的药敏分析,研究氧化苦参碱的抗肿瘤作用。通过蛋白质免疫印迹法和免疫荧光检测分析氧化苦参碱对β-连环蛋白的调节作用。采用β-连环蛋白过表达来确定β-连环蛋白在氧化苦参碱抑制肾细胞癌中的关键作用。此外,建立动物模型以研究氧化苦参碱对肿瘤生长的影响。

结果

氧化苦参碱抑制肾细胞癌进展,包括细胞增殖、凋亡、迁移、侵袭及化疗敏感性。进一步的机制研究表明,氧化苦参碱通过抑制β-连环蛋白的表达发挥其抗肿瘤作用。此外,在裸鼠模型中,氧化苦参碱对肿瘤生长表现出显著抑制作用,这与我们的体外实验结果一致。

结论

我们的研究结果表明氧化苦参碱是肾细胞癌的一种有效抗肿瘤药物,并提示其在肾细胞癌治疗中具有广阔的治疗应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41ca/7289957/609e3a4e3ad2/fphar-11-00808-g001.jpg

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