Studies on the Anti-Proliferative Effects and Molecular Mechanism of a Novel Small Molecular BOC26P in Breast Cancer

Background To explore the pharmacodynamic evaluation and mechanism research of BOC26P against breastcancer, and to provide a basis for the treatment of breast cancer.Method MTT assay was used to detect the cytotoxicity of BOC26P against 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231and MCF-7), and as well as the non-tumor cell lines MCF-10A, in variousdrug concentrations (from 0.004 to 1 μM). Western Blotting and Real-Time PCR assay were used to detect therelative protein and gene expression level after treatment with BOC26P in MCF-7/TAX. The effect of BOC26Pon Specific fluorescent P-gp substrate accumulation in MCF-7/TAX was analyzed by flow cytometry; Moleculardocking was used to analyze the binding capacity between BOC26P, Cyclosporine A, and Verapamil. FCM assaystaining with Annexin V-FITC/PI and Propidium iodide was used to measure the apoptosis and the cell cycleafter treatment with BOC26P in MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7; Detection ofmitochondrial membrane potential after treatment with BOC26P inMCF-7/TAX, MDA-MB-231/PT, MDA-MB231and MCF-7; Western Blotting and Real-Time PCR assay was used to detect the apoptosis relative proteinand gene expression level after treatment with BOC26P in MDA-MB-231, MCF-7, MDA-MB-231/PT, and MCF7/ADR.Results Cytotoxicity assay showed that BOC26P could effectively suppress 4 breast cancer cell lines (MCF7/TAX, MDA-MB-231/PT, MDA-MB-231, and MCF-7) with an IC50 value of under 0.5 μM. The IC50 value ofBOC26P on non-tumor cells MCF-10A was 32.29 μM. The binding ability of BOC26P to P-gp in breast cancercells was weak. There was no significant effect on the intracellular accumulation of Rhodamin 123(Rh123), Pgp binding specific fluorescence substrate, and multi-drug resistance protein P-gp expression in MCF-7/ADRand MDA-MB-231/PT tumor cells; BOC26P induced MCF-7/TAX, MDA-MB-231/PT, MDA-MB-231 and MCF-7cells cycle arrest at G2/M phase and lead to cell apoptosis. BOC26P induced significant activation of p53protein in MCF-7/ADR and MAD-MB-231/TAX cells. Under the same conditions, BOC26P promoted Baxexpression while inhibited Bcl-2 expression, and could significantly cause activation of Cleveland PARP andClevead Caspase3. The results demonstrated that BOC26P may induce apoptosis through the death receptorapoptosis pathway.Conclusion It is known that BOC26P has a significant proliferation inhibitory effect on breast cancer cellswithout serious side effects. BOC26P has the Potential to be developed into a clinical substitute drug for triple-

Spatial and Temporal Trend of Water Resources in Beijing, China during 1999-2012 and Its Impact Analysis.

Aims: The objective of this research is to understand and analyze the trend of water resources and its effects on land subsidence, vegetation cover change, and water supply reservoir drawdown in Beijing, China. Study Design: This research combined both field monitoring data and remote sensing data to study the water resource change and its impacts in the City of Beijing, China. Place and Duration of Study: This study water resource record data during 1999-2012 and the Landsat TM or ETM+ data in the same period to analyze the changes of water resources in the City of Beijing. The water level and water surface change of the Guanting Reservoir as a major urban water supply was analyzed since 1979 in confirmation of the trend of water resource change. Methodology: This research applied remote sensing data analysis, GIS spatial and spatial statistical analysis, and the conventional field monitoring data of water resources to understand and visualize the trend of water resource change and its environmental impacts in Beijing, China. Results: This research shows that both surface water and ground water resources are declining owing to the decrease of precipitation in Beijing. In the meantime, the proportion of agricultural and industrial water consumptions was gradually reduced and that of urban and domestic water consumptions continuously increased. Land subsidence spatially coincides with groundwater level decrease, and the maximum quantity could reach five meters. Vegetation cover and NDVI index showed high correlation with precipitation in mountainous region, but does not reflect the natural water supply in plain regions in Beijing. The surface water area in the Guanting Reservoir drastically reduced since 1979. Conclusion: The trend of water resource changes indicate that the water supply shortage in Beijing area was intensified. The more effective planning of economic development and urban growth in Beijing according its water resources is needed.