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Ye Y.,Pharmacology Laboratory of Traditional Chinese Medicine | Han X.,Pharmacology Laboratory of Traditional Chinese Medicine | Guo B.,Pharmacology Laboratory of Traditional Chinese Medicine | Sun Z.,Longhua Hospital | Liu S.,Pharmacology Laboratory of Traditional Chinese Medicine
Environmental Toxicology and Pharmacology | Year: 2013

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. μM osthole and 75. μM 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 TβRII, Smad2, Smad3 and Smad4 gene or protein expressions, as well as effectively blocked TGF-β-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 may be mediated by perturbations in the TGF-β/Smads pathway. © 2013 Elsevier B.V. Source

Ye Y.,Pharmacology Laboratory of Traditional Chinese Medicine | Liu S.,Pharmacology Laboratory of Traditional Chinese Medicine | Wu C.,Longhua Hospital | Sun Z.,Longhua Hospital
Journal of Molecular Histology | Year: 2015

The formation of tumor-promoting premetastatic microenvironment plays a pivotal role on metastatic progression. Understanding how the primary tumor can promote the formation of premetastatic microenvironment in the lung will aid discovery of a final cure for metastatic breast cancer. The murine 4T1 mammary carcinoma cells were injected into the mammary fat pads of the BALB/c mice. Days 0–14 were considered the premetastatic phase. Lung tissues were examined using hematoxylin-eosin staining and transmission electron microscopy. After intravenous injection of TGFβ1 pretreated 4T1 cells, the relative pulmonary vascular permeability was quantified, the extravasation, survival, and proliferation of tumor cells in premetastatic lungs were evaluated, and the levels of S100A8, S100A9, VEGF, and Angpt2 were detected in tumor-bearing mice. The results showed that during the premetastatic phase, an inflammatory response and inflammation-induced vascular hyperpermeability were established, leading to an abnormal pulmonary microenvironment, which facilitated extravasation of circulating tumor cells, and subsequent survival and proliferation of metastatic tumor cells in a TGFβ-dependent manner. Moreover, the expressions of S100A8, S100A9, VEGF, and Angpt2 were increased, and an induction of these genes by TGFβ was further observed in premetastatic lungs. Thus, this study demonstrated that TGFβ promoted the creation of premetastatic microenvironment by modulating certain crucial inflammatory cytokines and growth factors, and finally enhanced the ability of circulating cells to seed the lung. © 2015, Springer Science+Business Media Dordrecht. Source

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