Toxicologie : accès libre

Abstrait

Pharmacology and Toxicology of Anesthetics Adverse effects

Micael Holger

It's a remedial strategy for cancers including pancreatic to inhibit proteasome exertion. Disulfiram( DSF) may bind copper ( Cu) to form a DSF – Cu complex. DSF – Cu is able of converting apoptosis in cancer cells by inhibiting proteasome exertion. DSF is fleetly converted to diethyldithiocarbamate( DDTC) within bodies. copper( II) absorbed by bodies is reduced to copper ( I) when it enters cells. We set up that DDTC and copper ( I) could form a binuclear complex which might be entitled DDTC – Cu( I), and it had been synthesized by us in the laboratory. This study is to probe the anticancer eventuality of this complex on pancreatic cancer and the possible medium. Pancreatic cancer cell lines, SW1990, PANC- 1 and BXPC- 3 were used for in vitro assays. Womanish athymic raw mice grown SW1990 xenografts were used as beast models. Cell counting tackle- 8( cck- 8) assay and inflow cytometer were used for assaying apoptosis in cells. A 20S proteasome assay tackle was used in proteasome exertion analysis. Western spot ( WB) and immunohistochemistry( IHC) and terminal deoxynucleotidyl transferase dUTP nick end labeling( TUNEL) assays were used in excrescence sample analysis. The results suggest that DDTC – Cu ( I) inhibit pancreatic cancer cell proliferation and proteasome exertion in vitro and in vivo. Accumulation of ubiquitinated proteins, and increased p27 as well as dropped NF- κB expression were detected in excrescence apkins of DDTC – Cu( I)- treated group. Our data indicates that DDTC – Cu( I) is an effective proteasome exertion asset with the eventuality to be explored as a medicine for pancreatic cancer.