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Objective To evaluate the effects of Met inhibitor XL-880 on radiosensitivity of breast cancer cells MDA-MB-231.Methods MDA-MB-231 cell lines were assigned to the following treatment groups:control group,radiation group,XL-880 group and combination group.Cell apoptosis,cell cycle distributions and tumorigenicity were investigated by flow cytometry or clonogenic assay.The expression of apoptosis and cell cycle related proteins (p21,Cyclin B1,Bcl-2,Caspase-3 and PARP),and phosphorylation levels of c-Met were measured by Western blot.Results XL-880 combined with radiation significantly decreased the proliferation activity of MDA-MB-231 cells (P ＜ 0.05).Flow cytometry results showed that the rate of G2/M cell were increased with XL-880 (P ＜ 0.05),and the rate were (17.3 ±1.3) ％,(20.0 ± 4.0) ％,(28.5 ± 3.1) ％,(57.0 ± 3.3) ％,respectively.Annexin V/PI double-staining assay showed that XL-880 obviously induced the apoptosis of MDA-MB-231 cells after radiation (P ＜ 0.05),of which the apoptotic rates were (7.3 ±0.9)％,(14.1 ±0.6)％,(35.5 ±4.4)％,(48.2±5.3)％,respectively.XL-880 downregulated the expressions of Cyclin B1 and anti-apoptosis protein Bcl-2,while promoted the expression of apoptosis related protein cleaved Caspase-3 and PARP.Conclusions XL-880 enhance the radiosensitivity of breast cancer cell MDA-MB-231 by inhibiting Met pathway.
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Objective To investigate the clinicopathological characteristics and prognosis of lung metastases from breast cancer.Methods The clinical data of 119 breast cancer patients treated at our institution from January 2000 to January 2007 were retrospectively reviewed.Results Among 119 patients with lung metastasis,35.3％ was hormone receptor (HR) +/human epithelial growth factor receptor (HER2)-,17.6％ was HR +/HER2 +,21.8％ was HR-/HER2 + and 25.2％ was trriple negative breast cancer (TNBC).The rate of grade Ⅲ in triple negative breast cancer was higher than the other subtypes(P =0.016).The median overall survival was 60 months (9-141 months),the median time to lung metastases was 29 months (3-99 months),and the median survival after lung metastasis was 33 months (range,6-98 months).The 1-,2-,3-and 5-year survival rate was 72.9％,54.1％,35.1％ and 14.4％.Conclusions TNBC,number of lung metastases,time to lung metastases less than 24 months,and a history of systemic chemotherapy were important factors for prognosis of patients with lung metastases.
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Runt-related transcription factor 2 (Runx2) is a nuclear transcription factor of PEBP2/CBF superfamilies,and can regulate matrix metalloproteinase (MMP),osteopontin (OPN) and bone sialoprotein (BSP) which are associated with the metastasis of tumors including breast cancer and prostate cancer.In these cancers,the expression of Runx2 is highly up-regulated,which is closely correlated with the cell transformation and tumor progress.Lots of studies have demonstrated that the function of Runx2 is involved in several signal pathways activation,which can promote the early metastasis of malignant tumors.Therefore,the treatment targeting to Runx2 may be a new clinically choice to block the metastasis of tumors in the future.