The anti-tumor and mechanism of the benzoisoselenazolone derivatives on the human lung cancer adenocarcinoma A549 cells

Background:In this research,we investigated the anti-cancer effect and the related mechanism of 2-[2-(4-chlorobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(CTBO)and 2-[2-(4-nitrobenzamidomethylthio)-1,3,4-thiadiazol-5-yl]-1,2-benziselenazol-3(2H)-one compound(NTBO),which we synthesized in our lab previously.Methods:We applied the human lung cancer adenocarcinoma A549 cells to investigate the anti-tumor effect of CTBO and NTBO.The following methods were used in the research,including methylthiazolyldiphenyl-tetrazolium bromide assay,one-step terminal-deoxynucleotidyl transferase mediated nick end labeling,transcriptome sequencing analysis,quantitative reverse transcription polymerase chain reaction and western blot.Results:The results showed that both CTBO and NTBO significantly inhibited the A549 cells proliferation and induced the A549 cells apoptosis.The transcriptome sequencing analysis results illustrated that the two derivatives might exert the apoptotic effects through mitogen-activated protein kinase and tumor necrosis factor signaling pathways activation.Further,the western blot results suggested that CTBO and NTBO exerted anti-cancer effect through different molecular mechanisms.Conclusion:The results above provided fundamental research evidence for the further application of benziselenazolone derivatives in clinical.

Inhibition Mechanism of Qingluo Tongbi Granule(清络通痹颗粒)on Osteoclast Differentiation Induced by Synovial Fibroblast and Monocytes Co-Culture in Adjuvant-Induced Arthritic Rats

Objective： To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule （清络通痹颗粒, QTG） on osteoclast differentiation in rheumatoid arthritis in rats. Methods： Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic （AIA） rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptorassociated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 （TRAF6/ MAPK/NFATcl） pathways was examined. Results： The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase （TRAP） staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase （ERK）1/2, c-Jun N-terminal kinase （JNK） and p38 and decreased the percentage of cells with nuclear NFATcl in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity （P〈0.01 and P〈0.05, respectively）. After the addition of MAPK inhibitors, the NFATcl expression showed no significant difference compared with the control group （P〉0.05）. Conclusions： Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATcl pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.