Combination treatment with platycodin D and osthole inhibits cell proliferation and invasion in mammary carcinoma cell lines

In this study, two invasive mammary carcinoma cells (MDA-MB-231 and 4T1) were utilized to evaluate the inhibitory activities of platycodin D, osthole, and the two in combination. The anti-proliferative effect was tested using the MTT and BrdU assay, and the combination of 15 mu M osthole and 75 mu M platycodin D was used for subsequent analyses. The anti-invasive effect was evaluated by the transwell assay. The results showed that the combination treatment reduced both cell proliferation and invasion. Western blot and real-time PCR revealed that the platycodin D-osthole combination significantly decreased T beta RII, Smad2, Smad3 and Smad4 gene or protein expressions, as well as effectively blocked TGF-beta-induced phosphorylation of Smad2 and Smad3. Thus, this study demonstrates that the anti-cancer effects of the platycodin D-osthole combination in breast cancer cells involve proliferation inhibition and invasion blockade, both of which maybe mediated by perturbations in the TGF-beta/Smads pathway. (C) 2013 Elsevier B.V. All rights reserved.