ArticleJournal of cancer research and clinical oncology2012
Effects of CDC7 gene silencing and Rituximab on apoptosis in diffuse large B cell lymphoma cells.
Article in Journal of cancer research and clinical oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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3 authors at 1 institution in 1 country.
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Abstract
backgroundThe cell division cycle 7 (CDC7) is a serine-threonine kinase, which is required for DNA replication and is high expressed in diffuse large B cell lymphoma (DLBCL).
methodsIn this study, we targeted CDC7 in human DLBCL-ABC subtype cells (ly3) and examined the subsequent alterations in cellular apoptosis. The expression of CDC7 was silenced with small interfering RNA (siRNA)-expressing plasmid. CDC7 gene silencing cells were then incubated with or without rituximab for 24 h. Following treatment, Annexin V/propidium iodide staining followed by flow cytometry was used to examine cellular apoptosis. Furthermore, the expression of caspase 3, Bax, and Bcl-2 protein was analyzed by Western blotting. The expression of Bax and Bcl-2 mRNA was analyzed by quantitative real-time PCR.
resultsCompared to non-treated or control siRNA-transfected cells, significantly higher levels of apoptosis were detected in siCDC7-transfected cells and rituximab-treated cells (P < 0.05), which was further enhanced in CDC7-targeted cells with rituximab treatment (P < 0.05). The pro-apoptotic effects were accompanied with up-regulation of caspase 3 and Bax, meanwhile down-regulation of Bcl-2.
conclusionCombined treatments using rituximab and CDC7 gene silencing significantly increases apoptosis in ly3 cells and plays synergistic effect. CDC7 is a novel therapeutic target in DLBCL patients. CDC7 inhibitors combined with rituximab will be the new therapy for the ABC-DLBCL patients.
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