Mda-7/IL-24 induces the differentiation of B cell lymphoma via activation of P38 MAPK signalling pathway
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摘要
Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the differentiation of B cell lymphoma is not yet clear. This study investigated the effects of Mda-7/IL-24 overexpression on the differentiation of human B cell lymphoma as well as its mechanism of action. The proliferation of stable Mda-7/IL-24 overexpressing Raji and Daudi cells was assessed by the MTS method. Cell cycle distribution, apoptosis and the immunophenotype of Raji and Daudi cells were assayed by flow cytometry(FCM). The expression of Blimp1 and Bcl6 were analyzed by western blotting. In addition, western blotting analysis assay were used to investigate the effect of Mda-7/IL-24 on activity of P38 MAPK signalling pathway in Raji and Daudi cells. Growth of Mda-7/IL-24 overexpressing Raji and Daudi cells was inhibited significantly, compared with those of non-transfected cells and cells transfected with vector alone. The cell cycle is arrested in G1 phase and apoptosis is not involved in the growth inhibition of Raji and Daui cells overpressing Mda-7/IL-24. Overexpressing Mda-7/IL-24 resulted in the significantly decreased expression of CD10, and increased expression of CD45 and CD138 in cell surface of Raji and Daudi cells. The expression of Blimp1 was higher, while the levels of Bcl6 protein was lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Futhermore, the activities of P38 MAPK signalling pathway in Raji and Daudi cells were upregulated. These results indicated that Mda-7/IL-24 could induce terminal differentiation of B lymphoma cells by altering the expression of Blimp1 and Bcl6 via regulating P38 MAPK signalling pathway, suggesting that Mda-7/IL-24 may therefore be a potential candidate for differentiation treatment of B cell lymphomas.
Mda-7/IL-24 has been shown to inhibit the proliferation of various human tumor cell lines, but its effect on the differentiation of B cell lymphoma is not yet clear. This study investigated the effects of Mda-7/IL-24 overexpression on the differentiation of human B cell lymphoma as well as its mechanism of action. The proliferation of stable Mda-7/IL-24 overexpressing Raji and Daudi cells was assessed by the MTS method. Cell cycle distribution, apoptosis and the immunophenotype of Raji and Daudi cells were assayed by flow cytometry(FCM). The expression of Blimp1 and Bcl6 were analyzed by western blotting. In addition, western blotting analysis assay were used to investigate the effect of Mda-7/IL-24 on activity of P38 MAPK signalling pathway in Raji and Daudi cells. Growth of Mda-7/IL-24 overexpressing Raji and Daudi cells was inhibited significantly, compared with those of non-transfected cells and cells transfected with vector alone. The cell cycle is arrested in G1 phase and apoptosis is not involved in the growth inhibition of Raji and Daui cells overpressing Mda-7/IL-24. Overexpressing Mda-7/IL-24 resulted in the significantly decreased expression of CD10, and increased expression of CD45 and CD138 in cell surface of Raji and Daudi cells. The expression of Blimp1 was higher, while the levels of Bcl6 protein was lower, in Mda-7/IL-24 overexpressing Raji and Daudi cells. Futhermore, the activities of P38 MAPK signalling pathway in Raji and Daudi cells were upregulated. These results indicated that Mda-7/IL-24 could induce terminal differentiation of B lymphoma cells by altering the expression of Blimp1 and Bcl6 via regulating P38 MAPK signalling pathway, suggesting that Mda-7/IL-24 may therefore be a potential candidate for differentiation treatment of B cell lymphomas.
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