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

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-[beta]/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-[beta]/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-[beta]1 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-[beta]1/Smads-PAI-1 signaling pathway, suggesting it as a promising agent in treating colorectal cancer. Keywords: oridonin, colon cancer, TGF-[beta]/Smads pathway, PAI-1