The inhibitory effect of oridonin on colon cancer was mediated by deactivation of TGF-β1/Smads-PAI-1 signaling pathway in vitro and vivo

冬凌草甲素对结肠癌的抑制作用是通过抑制TGF-β1/Smads-PAI-1信号通路在体内和体外发挥作用的

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作者:He-Qi Bu, Feng Shen, Junhui Cui

Background

Oridonin, the main active component of Rabdosia rubescens, has been demonstrated to have anti-tumor effect on all kinds of cancer cells through various mechanisms and it has shown antitumor activity in some tumors partially via the suppression of TGF-β/Smads signaling pathway. The

Conclusion

Our present study demonstrated that the growth inhibition of colon cancer by oridonin could be partially mediated through discontinuing TGF-β1/Smads-PAI-1 signaling pathway, suggesting it as a promising agent in treating colorectal cancer.

Methods

CCK-8 assay was employed to assess cell viability. The key target genes and proteins involved in TGF-β/Smads pathway was detected by RT-PCR, Western blotting and immunohistochemistry. The orthotopic transplantation tumor model of colon cance LOVO cell was introduced to detect anti-cancer effects in vivo.

Results

Oridonin inhibited the proliferation of colon cancer LOVO cells in a concentration and time dependent manner. In addition, oridonin reduced the levels of Smad2, Smad3, Smad4, PAI-1 and the phosphorylation of Smad2 and Smad3 induced by TGF-β1 in vitro. Subsequently, we established an orthotopically implanted tumor model in nude mice and found that oridonin treatment significantly suppressed tumor growth, and which was accompanied by the down-regulation of Smad2, Smad3, Smad4, PAI-1 and p-Smad2, p-Smad3 expression levels.

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