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雷公藤红素通过TGF-β1/Smad信号通路抑制结直肠癌。

Celastrol inhibits colorectal cancer through TGF-β1/Smad signaling.

作者信息

Jiang Zhitao, Cao Qianyu, Dai Guoliang, Wang Jianchun, Liu Chundi, Lv Lingyan, Pan Jinhuo

机构信息

Department of Pharmacy Office, Zhangjiagang Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, China.

The First Clinical College, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Onco Targets Ther. 2019 Jan 9;12:509-518. doi: 10.2147/OTT.S187817. eCollection 2019.

Abstract

BACKGROUND

There are few clinical challenges associated with the treatment of colorectal cancer (CRC). Studies have shown that TGF-β plays a crucial role in CRC. Importantly, celastrol, a major components of the root extract of the traditional Chinese herb , has been shown to inhibit the growth, adhesion, and metastasis of human CRC cells through the inhibition of TGF-β1/Smad signaling.

MATERIALS AND METHODS

Real-time PCR and Western blot tests were proceeded to present TGF-β1, TGF-β receptor type I (TGFβRI), TGF-β receptor type II (TGFβRII), Smad2/3, p-Smad2/3, Smad4, and glyceraldehyde-3-phosphate dehydrogenase expression in human colon cancer cell samples.

RESULTS

Our results indicated that celastrol can reduce the expression levels of TGF-β1, TGFβRI, and TGFβRII in HCT116 and SW620 cells. Furthermore, celastrol could also prevent the increase in Smad4 and p-Smad2/3 in HCT116 and SW620 cells.

CONCLUSION

Celastrol could inhibit tumor growth through TGF-β1/Smad signaling and might be a promising therapeutic component against CRC.

摘要

背景

结直肠癌(CRC)的治疗面临一些临床挑战。研究表明,转化生长因子-β(TGF-β)在结直肠癌中起关键作用。重要的是,中药根提取物的主要成分雷公藤红素已被证明可通过抑制TGF-β1/Smad信号通路来抑制人结直肠癌细胞的生长、黏附和转移。

材料与方法

采用实时聚合酶链反应(PCR)和蛋白质免疫印迹法检测人结肠癌细胞样本中TGF-β1、I型TGF-β受体(TGFβRI)、II型TGF-β受体(TGFβRII)、Smad2/3、磷酸化Smad2/3(p-Smad2/3)、Smad4和甘油醛-3-磷酸脱氢酶的表达。

结果

我们的结果表明,雷公藤红素可降低HCT116和SW620细胞中TGF-β1、TGFβRI和TGFβRII的表达水平。此外,雷公藤红素还可抑制HCT116和SW620细胞中Smad4和p-Smad2/3的增加。

结论

雷公藤红素可通过TGF-β1/Smad信号通路抑制肿瘤生长,可能是一种有前景的抗结直肠癌治疗成分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc29/6331187/58792d9c23f2/ott-12-509Fig1.jpg

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