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Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-induced apoptosis of human esophageal squamous cell carcinoma cells.

Dang L, Wen F, Yang Y, Liu D, Wu K, Qi Y, Li X, Zhao J, Zhu D, Zhang C, Zhao S - Int. J. Mol. Med. (2014)

Bottom Line: Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner.MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8.These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Physical Examination Centre, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

ABSTRACT
Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.

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Related in: MedlinePlus

Proteasome inhibitor MG132 significantly decreased the cell viability in EC9706 cells in a dose- and time-dependent manner. (a) EC9706 cells were treated with or without various concentrations of MG132 as indicated for 12, 24 and 36 h. (b) EC9706 cells were treated with 1, 5 and 10 μM for 12, 24, 36, 48, 60 and 72 h.
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f1-ijmm-33-05-1083: Proteasome inhibitor MG132 significantly decreased the cell viability in EC9706 cells in a dose- and time-dependent manner. (a) EC9706 cells were treated with or without various concentrations of MG132 as indicated for 12, 24 and 36 h. (b) EC9706 cells were treated with 1, 5 and 10 μM for 12, 24, 36, 48, 60 and 72 h.

Mentions: A dose-dependent study of EC9706 cells exposed to various concentrations of MG132 for 12, 24 and 36 h is shown in Fig. 1a; the modest degrees of growth inhibition were noted at a concentration of 2 μM, which increased substantially at a concentration of 4 μM. These events were significantly increased at a concentration of 10 μM. A time-course study of cells exposed to MG132 revealed a significant increase in cell viability as early as 24 h, and reached near-maximal levels after 60 h (Fig. 1b).


Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-induced apoptosis of human esophageal squamous cell carcinoma cells.

Dang L, Wen F, Yang Y, Liu D, Wu K, Qi Y, Li X, Zhao J, Zhu D, Zhang C, Zhao S - Int. J. Mol. Med. (2014)

Proteasome inhibitor MG132 significantly decreased the cell viability in EC9706 cells in a dose- and time-dependent manner. (a) EC9706 cells were treated with or without various concentrations of MG132 as indicated for 12, 24 and 36 h. (b) EC9706 cells were treated with 1, 5 and 10 μM for 12, 24, 36, 48, 60 and 72 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4020493&req=5

f1-ijmm-33-05-1083: Proteasome inhibitor MG132 significantly decreased the cell viability in EC9706 cells in a dose- and time-dependent manner. (a) EC9706 cells were treated with or without various concentrations of MG132 as indicated for 12, 24 and 36 h. (b) EC9706 cells were treated with 1, 5 and 10 μM for 12, 24, 36, 48, 60 and 72 h.
Mentions: A dose-dependent study of EC9706 cells exposed to various concentrations of MG132 for 12, 24 and 36 h is shown in Fig. 1a; the modest degrees of growth inhibition were noted at a concentration of 2 μM, which increased substantially at a concentration of 4 μM. These events were significantly increased at a concentration of 10 μM. A time-course study of cells exposed to MG132 revealed a significant increase in cell viability as early as 24 h, and reached near-maximal levels after 60 h (Fig. 1b).

Bottom Line: Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner.MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8.These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Physical Examination Centre, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.

ABSTRACT
Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.

Show MeSH
Related in: MedlinePlus