RESUMO
Auranofin has been developed as antirheumatic drugs, which is currently under clinical development for the treatment of chronic lymphocytic leukemia. Previous report showed that auranofin induced apoptosis by enhancement of annexin A5 expression in PC-3 cells. To understand the role of annexin A5 in auranofin-mediated apoptosis, we performed microarray data analysis to study annexin A5-controlled gene expression in annexin A5 knockdown PC-3 cells. Of differentially expressed genes, plasminogen activator inhibitor (PAI)-2 was increased by annexin A5 siRNA confirmed by qRT-PCR and western blot. Treatment with auranofin decreased PAI-2 and increased annexin A5 expression as well as promoting apoptosis. Furthermore, auranofin-induced apoptosis was recovered by annexin A5 siRNA but it was promoted by PAI-2 siRNA. Interestingly, knockdown of annexin A5 rescued PAI-2 expression suppressed by auranofin. Taken together, our study suggests that induction of annexin A5 by auranofin may enhance apoptosis through suppression of PAI-2 expression in PC-3 cells.
Assuntos
Humanos , Anexina A5 , Antirreumáticos , Apoptose , Auranofina , Western Blotting , Expressão Gênica , Leucemia Linfocítica Crônica de Células B , Inibidor 2 de Ativador de Plasminogênio , Ativadores de Plasminogênio , Plasminogênio , Próstata , Neoplasias da Próstata , RNA Interferente Pequeno , Estatística como AssuntoRESUMO
Objective To investigate the regulatory effect of TNF ? on the expression of plasminogen activator inhibitor 2(PAI 2) and its biological significance. Methods Using immunocytochemistry(ICC), terminal deoxynucleotidyl transferase mediated end labeling (TUNEL) and ICC/TUNEL double label methods, the expression of PAI 2 in and the apoptosis of the cultured epidermal keratinocytes treated by TNF ? were detected. Results After the mouse epidermal keratinocytes were incubated with TNF ?, compared with the unshed cells, the expression of PAI 2 in shed cells and the cellular apoptosis increased obviously. The increased PAI 2 expression also appeared in the apoptotic cells, especially in larger and multi angled apoptotic cells. Conclusion In highly differentiated epidermal keratinocytes, TNF ? can enhance the expression of PAI 2 as well as apoptosis. Furthermore, according to the relation with the keratinocytes apoptosis, there are two types of PAI 2 induced by TNF ?, one of which is related to apoptosis, but the other is not.