Anti-tumor Effect of Piceatannol on Triple Negative Breast Cancer Cell Line MDA-MB-468 and Its Mechanism / 中国实验方剂学杂志

Objective:To investigate the effect of piceatannol （PIC） on the proliferation， apoptosis and cell cycle of MDA-MB-468 triple negative breast cancer cells and its mechanism. Method:The methylthiazolyldiphenyl-tetrazoliu bromide （MTT） colcorimetry method was used to investigate the effect of different concentrations of PIC （0， 2.5， 5.0， 10.0， 20.0， 40.0， 80.0， 160.0 μmol·L^-1） on the cell viabilities of triple negative breast cancer MDA-MB-468 cells and calculate the half maximal inhibitory concentration （IC₅₀） value， the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the cell cycle of MDA-MB-468 were investigated by flow cytometry with propidium iodide （PI） staining. The apoptotic effect of PIC （5.0， 10.0， 20.0 μmol·L^-1） on MDA-MB-468 cells in triple negative breast cancer was investigated by flow cytometry with cell apoptosis detection Annexin V-FITC and PI double staining. Western blot was used to investigate the effect of different concentrations of PIC （5.0， 10.0， 20.0 μmol·L^-1） on the proliferation and apoptosis of MDA-MB-468 cells and detect the expressions ofsecreted glycoprotein Wnt/<italic>β</italic>-catenin pathway related proteins. Result:MTT results showed that compared with the blank group， PIC could inhibit the proliferation of MDA-MB-468 cells in a concentration-dependent manner （<italic>P</italic><0.05， <italic>P</italic><0.01）， with IC₅₀ at（39.4±4.6）μmol·L^-1. Compared with the blank group， PIC could increase the percentage of MDA-MB-468 cells in G₀/G₁ phase about cell cycle in a concentration-dependent manner （<italic>P</italic><0.01）. Compared with the blank group， 5.0， 10.0， 20.0 μmol·L^-1 PIC could induce apoptosis of MDA-MB-468 cells for 48 h（<italic>P</italic><0.01）， and the apoptosis rate of MDA-MB-468 cells reached 49.87% when treated with 20.0 μmol·L^-1 for 48 h. Compared with the blank group， PIC could significantly reduce the expressions of <italic>β</italic>-catenin， proto-oncogene （C-myc） and adhesion factor （CD44） proteins in MDA-MB-468 cells， significantly inhibit the phosphorylation of<italic> </italic>protein kinase B （Akt） and p38 mitogen activated protein kinase （p38 MAPK） proteins and the protein expression of B lymphocyte tumor-2 （Bcl-2）， and enhance cysteine aspartic acid protease-3 （Caspase-3）， Bcl-2 related X protein （Bax） and phosphorylated <italic>β</italic>-catenin protein expression（<italic>P</italic><0.01）. Conclusion:PIC may inhibit the proliferation of MDA-MB-468 cells by inhibiting the Wnt/<italic>β</italic>-catenin signaling pathway， block the cell cycle in G0/G1 phase， and induce its apoptosis.

Anti-breast Cancer Activities in Vitro of Oxymatrine Combined with Bevacizumab： An Exploration Focusing on EMT Regulation Through Wnt/β-catenin / 中国实验方剂学杂志

Objective:To observe the effect of oxymatrine （OM） combined with bevacizumab （ BV ） on the proliferation， invasion， and migration of breast cancer MCF-7 cells and explore the mechanism of OM in regulating BV-induced epithelial-mesenchymal transition （EMT） based on the Wnt/<italic>β</italic>-catenin signaling pathway. Method:The effect of different concentrations of OM（0， 0.5， 1.0， 2.0， 4.0， 8.0， 16.0 mmol·L^-1）and BV（0， 0.25×10^-4， 0.50×10^-4， 1.00×10^-4， 2.00×10^-4， 4.00×10^-4， and 8.00×10^-4 mmol·L^-1）on the proliferation of MCF-7 cells were detected by cell counting kit-8（CCK-8）assay. The effect of OM（4.0 mmol·L^-1） combined with BV（2.00×10^-4 mmol·L^-1）on the invasion and migration of MCF-7 cells were observed in transwell and scratch repair tests. Western blot was conducted to investigate the effect of OM（4.0 mmol·L^-1）combined with BV （2.00×10^-4 mmol·L^-1） on proliferation-related proteins in MCF-7 cells， followed by the detection of the expression levels of Wnt/<italic>β</italic>-catenin signaling pathway- and EMT-related proteins. Result:Compared with the blank group， OM （2.0，4.0，8.0，16.0 mmol·L^-1） inhibited the proliferation of MCF-7 cells in a concentration-dependent manner （<italic>P</italic><0.01）， while BV did not show the inhibitory effect against the proliferation of MCF-7 cells. The inhibitory effect of the combination of the two drugs on the proliferation of MCF-7 cells was not significantly different from that of OM. Compared with the blank group， OM significantly reduced the migration distance of MCF-7 cells and the number of invaded cells（<italic>P</italic><0.01）， while BV increased the migration distance of MCF-7 cells and the number of invaded cells （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with BV， its combination with OM significantly inhibited the invasion and migration of MCF-7 cells induced by BV （<italic>P</italic><0.01）. Compared with the blank group， both OM and the combined medication obviously inhibited the phosphorylation of proliferation-related protein kinase B（Akt） and extracellular-signal-regulated protein kinase 1/2 （ERK1/2）in MCF-7 cells （<italic>P</italic><0.01） and down-regulated the protein expression levels of <italic>β</italic>-catenin， proto-oncogene （c-Myc）， CD44， and G₁/S-specific cyclin D₁ in Wnt/<italic>β</italic>-catenin signaling pathway （<italic>P</italic><0.05，<italic>P</italic><0.01）. Besides， OM and the combination of two drugs both significantly reduced the protein expression levels of calcium-dependent cell adhesion protein <italic>N</italic>-cadherin and Vimentin in EMT， whereas increased the expression of calcium-dependent cell adhesion protein E-cadherin（<italic>P</italic><0.01）. However， the expression of the above-mentioned proteins in the BV group was reversed （<italic>P</italic><0.05，<italic>P</italic><0.01）. Conclusion:After the combination with BV， OM plays an anti-breast cancer role by effectively inhibiting the activation of Wnt/<italic>β</italic>-catenin pathway induced by BV and reversing EMT.

Nanosecond square high voltage pulse generator for electro-optic switch.

A scalable square high voltage pulse generator, which has the properties of fast rise time, fast fall time, powerful driving capability, and long lifetime, is presented in this paper by utilizing solid state circuitry. A totem-pole topology is designed to supply a powerful driving capability for the electro-optic (EO) crystal which is of capacitive load. Power MOSFETs are configured in series to sustain high voltage, and proper driving circuits are introduced for the specific MOSFETs configurations. A 3000 V pulse generator with ~49.04 ns rise time and ~10.40 ns fall time of the output waveform is presented. This kind of generator is desirable for electro-optic switch. However, it is not specific to EO switch and may have broad applications where high voltage fast switching is required.