ABSTRACT
Nowadays, it is still technologically challenging to prepare highly sensitive sensing films using microelectrical mechanical system (MEMS) compatible methods for miniaturized sensors with low power consumption and high yield. Here, sensitive cross-linked SnO2:NiO networks were successfully fabricated by sputtering SnO2:NiO target onto the etched self-assembled triangle polystyrene (PS) microsphere arrays and then ultrasonically removing the PS microsphere templates in acetone. The optimum line width (~ 600 nm) and film thickness (~ 50 nm) of SnO2:NiO networks were obtained by varying the plasma etching time and the sputtering time. Then, thermal annealing at 500 °C in H2 was implemented to activate and reorganize the as-deposited amorphous SnO2:NiO thin films. Compared with continuous SnO2:NiO thin film counterparts, these cross-linked films show the highest response of ~ 9 to 50 ppm ethanol, low detection limits (< 5 ppm) at 300 °C, and also high selectivity against NO2, SO2, NH3, C7H8, and acetone. The gas-sensing enhancement could be mainly attributed to the creating of more active adsorption sites by increased stepped surface in cross-linked SnO2:NiO network. Furthermore, this method is MEMS compatible and of generality to effectively fabricate other cross-linked sensing films, showing the promising potency in the production of low energy consumption and wafer-scale MEMS gas sensors.
ABSTRACT
Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer (CRC) and to investigate their anti-metastatic mechanisms. In this study, six CRC cell lines were used. We showed that YH-306 significantly inhibited the migration and invasion of CRC cells in a dose-dependent manner. In addition, YH-306 inhibited cell adhesion and protrusion formation of HCT116 and HT-29 CRC cells. Moreover, YH-306 potently suppressed uninhibited proliferation in all six CRC cell lines tested and induced cell apoptosis in four cell lines. Furthermore, YH-306 inhibited CRC colonization in vitro and suppressed CRC growth in a xenograft mouse model, as well as hepatic/pulmonary metastasis in vivo. YH-306 suppressed the activation of focal adhesion kinase (FAK), c-Src, paxillin, and phosphatidylinositol 3-kinases (PI3K), Rac1 and the expression of matrix metalloproteases (MMP) 2 and MMP9. Meanwhile, YH-306 also inhibited actin-related protein (Arp2/3) complex-mediated actin polymerization. Taken together, YH-306 is a candidate drug in preventing growth and metastasis of CRC by modulating FAK signalling pathway.
Subject(s)
Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Neoplasm Metastasis/drug therapy , Signal Transduction/drug effects , Small Molecule Libraries/pharmacology , Animals , Cell Line, Tumor , Colorectal Neoplasms/metabolism , HCT116 Cells , HT29 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, NudeABSTRACT
The transforming growth factor beta (TGFß) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGFß signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-ß-carboline derivatives from virtual screening which potentially inhibit the TGFß signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-ß-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGFß signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.
