RESUMO
In this work, a series of dibenzimidazole derivatives 1-4, act as highly reversible colorimetric and fluorescent pH chemosensor, were designed and synthesized. Excellent reversible pH response of these sensors could be found by a specific pH change through obvious fluorescent color changes. The response is not affected by common cations (including Al3+, Cu2+, Ca2+, Cd2+, Co2+, Cr3+, Mg2+, Na+, K+, Ni2+, Pb2+ and Zn2+) and anions (including F-, Cl-, Br-, I-, ClO4-, H2PO4-, HSO4-, HCO3- and CH3COO-). Notably, these sensors can be reused more than 10 times without losing functionality. Unlike previous reports, the distinct properties of 1-4 are attributed to the varied link groups. Based on comprehensive experimental data and mechanistic analyses, it is concluded that sensors 1-4 are promising candidates for use as highly reversible "on-off-on" fluorescence switches under precise pH control.
RESUMO
BACKGROUND: Wnt/beta-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/beta-catenin pathway modification of the cellular apoptosis. METHODS: To identify potential genes regulated by Wnt/beta-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of beta-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR. RESULTS: Stably integrated inducible RNAi vector could effectively suppress beta-catenin expression and the transcriptional activity of beta-catenin/TCF. Meanwhile, depletion of beta-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-kappaB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of beta-catenin. CONCLUSION: Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/beta-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified beta-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.