OncoTargets and Therapy (Sep 2019)
The inhibitory effect of oridonin on colon cancer was mediated by deactivation of TGF-β1/Smads-PAI-1 signaling pathway in vitro and vivo
Abstract
He-Qi Bu, Feng Shen, Junhui Cui Department of Coloproctological Surgery, Tongde Hospital of Zhejiang Province, Hangzhou 310012, People’s Republic of ChinaCorrespondence: Junhui CuiDepartment of Coloproctological Surgery, Tongde Hospital of Zhejiang Province, 234 Gu-Cui Road, Hangzhou 310012, People’s Republic of ChinaTel/Fax +86 571 8997 2373Email [email protected]: 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 aim of this study was to explore the anticancer effect of oridonin on human colon carcinoma and underlying mechanism in vitro and vivo.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.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.Keywords: oridonin, colon cancer, TGF-β/Smads pathway, PAI-1
