To explore potential therapeutic strategies for interrupting the interleukin-6 (IL-6) signaling pathway, we measured IL-6 expression in ovarian cancer tissues, and evaluated the effects of a monoclonal anti-IL-6 antibody; siltuximab (CNTO 328), on levels of IL-6-induced Stat3 phosphorylation, Stat3 nuclear translocation, and Stat3 downstream antiapoptotic genes. We then looked for enhancing paclitaxel sensitivity in multidrug-resistant ovarian cancer cell lines. Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry. Effects of siltuximab on IL-6-induced activation of Stat3 in an ovarian cancer cell line were determined by Western blot and real-time analysis of Stat3 nucleocytoplasmic translocation. Influence of combination of siltuximab and paclitaxel on tumor growth was evaluated in a xenograft mouse mode in vivo. Metastatic and drug-resistant recurrent tumors have significantly higher IL-6 expression when compared with the matched primary tumors. Siltuximab specifically suppressed IL-6-induced Stat3 phosphorylation and Stat3 nuclear translocation. Treatment with siltuximab significantly decreased the levels of Stat3 downstream proteins such as MCL-1, Bcl-X(L), and survivin. Treatment with siltuximab reduced expression of multiple IL-6-induced genes in these cell lines. Furthermore, siltuximab increased the cytotoxic effects of paclitaxel in a paclitaxel resistant ovarian cancer cell line in vitro, but combination therapy with siltuximab did not have a significant effect on paclitaxel resistant tumor growth in vivo. These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression. Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer.
To explore potential therapeutic strategies for interrupting the interleukin-6 ( IL-6 ) signaling pathway , we measured IL-6 expression in ovarian cancer tissues , and evaluated the effects of a monoclonal anti - IL-6 antibody ; siltuximab ( CNTO 328 ) , on levels of IL-6-induced Stat3 phosphorylation , Stat3 nuclear translocation , and Stat3 downstream antiapoptotic genes . We then looked for enhancing paclitaxel sensitivity in multidrug - resistant ovarian cancer cell lines . Expressions of IL-6 in ovarian cancer patient specimens were assessed by immunohistochemistry . Effects of siltuximab on IL-6-induced activation of Stat3 in an ovarian cancer cell line were determined by Western blot and real - time analysis of Stat3 nucleocytoplasmic translocation . Influence of combination of siltuximab and paclitaxel on tumor growth was evaluated in a xenograft mouse mode in vivo . Metastatic and drug - resistant recurrent tumors have significantly higher IL-6 expression when compared with the matched primary tumors . Siltuximab specifically suppressed IL-6-induced Stat3 phosphorylation and Stat3 nuclear translocation . Treatment with siltuximab significantly decreased the levels of Stat3 downstream proteins such as MCL-1 , Bcl - X(L ) , and survivin . Treatment with siltuximab reduced expression of multiple IL-6-induced genes in these cell lines . Furthermore , siltuximab increased the cytotoxic effects of paclitaxel in a paclitaxel resistant ovarian cancer cell line in vitro , but combination therapy with siltuximab did not have a significant effect on paclitaxel resistant tumor growth in vivo . These results show that siltuximab effectively block the IL-6 signaling pathways and IL-6-induced gene expression . Blockage of IL-6 signaling may provide benefits for the treatment of ovarian cancer .
Which interleukin is blocked by Siltuximab?
Which interleukin is blocked by Siltuximab ?
interleukin-6
interleukin-6