Regulation of extrinsic apoptotic signaling by c-FLIP: towards targeting cancer networks

Abstract Background This study focuses on the application of Provan and Kenis’ modes of network governance to the specific field of public healthcare networks, extending the framework to an analysis of systems in which networks are involved. Thus, the aim of this study is to analyze and compare the governance of two cancer networks in two Italian regions that underwent system reconfiguration processes due to reforms in the healthcare system. Methods A qualitative study of two clinical networks in the Italian healthcare system was conducted. The sample for interviews included representatives of the regional administration (n = 4), network coordinators (n = 6), and general and clinical directors of health organizations involved in the two networks (n = 25). Data were collected using semi-structured interviews. Results Our study shows that healthcare system reforms have a limited impact on network governance structures. In fact, strong inertial tendencies characterize networks, especially network administrative organization models (NAO). Networks tend to find their own balance with respect to the trade-offs analyzed using a mix of formal and informal ties. Our study confirms the general validity of Provan and Kenis’ framework and shows how other specific factors and contingencies may affect the possibility that cancer networks find positive equilibria between competing needs of inclusivity and efficiency, internal and external legitimacy, and stability and flexibility. It also shows how networks react to external changes. Conclusions Our study shows the importance of considering three factors and contingencies that may affect network effectiveness: a) the importance of looking at network governance modes not in isolation, but in relationship to the governance of regional systems; b) the influence of a specific network’s governance structure on the network’s ability to respond to tensions and to achieve its goals; and c) the need to take into account the role of professionals in network governance.

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Proteasome inhibitor MG132 induces apoptosis in human osteosarcoma U2OS cells

Human & Experimental Toxicology ◽

10.1177/09603271211017972 ◽

2021 ◽

pp. 096032712110179

Author(s):

Han Ki Lee ◽

See-Hyoung Park ◽

Myeong Jin Nam

Keyword(s):

Signaling Pathways ◽

Proteasome Inhibitor ◽

Migration And Invasion ◽

Apoptotic Signaling ◽

Antiapoptotic Proteins ◽

Human Osteosarcoma ◽

Anticancer Effects ◽

Caspase 7 ◽

U2os Cells ◽

Western Blotting Assay

MG132 is a potent, reversible, and cell-permeable 20S proteasome inhibitor and it is derived from a Chinese medicinal plant. The purpose of this study is to investigate the anticancer effects of MG132 against human osteosarcoma U2OS cells. We first performed MTT and colony formation assays to investigate the anti-proliferative effects of MG132. The results demonstrated that MG132 suppressed the proliferation of U2OS cells. Furthermore, we found that treatment with MG132 increased apoptosis and induced DNA damage in U2OS cells. Additionally, zymography, wound healing, and invasion assays showed that MG132 suppressed the enzymatic activity of matrix metalloproteinases, cell migration, and invasion, respectively of U2OS cells. Furthermore, western blotting assay was performed to investigate the apoptotic signaling pathways in MG132-treated U2OS cells. Our results showed that MG132 downregulated the expression of antiapoptotic proteins, including CDK2, CDK4, Bcl-xL, and Bcl-2, whereas it upregulated the expression of proapoptotic proteins, including p21, p27, p53, p-p53 (ser15, ser20, and ser46), cleaved forms of caspase-3, caspase-7, caspase-9, and PARP, and FOXO3 in U2OS cells. These results demonstrated that MG132 activated apoptotic signaling pathways in U2OS cells. Interestingly, MG132 downregulated the phosphorylation of Akt and Erk. Taken together, our results suggest that MG132 has anticancer effects in U2OS cells. Therefore, MG132 may be a potential therapeutic agent for the treatment of osteosarcoma.

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