Figure 6. SOCS3 expression or IL6 blockade inhibits tumor growth and reduces circulating tumor cells in mice bearing MCF10Ap53⁻PTEN⁻ xenografts.

(a) Expressions of SOCS3, phosphorylated NF-κB and phosphorylated Stat3 are analyzed by western blotting in MCF10A, MCF10Ap53⁻PTEN⁻ and SOCS3 overexpressing MCF10Ap53⁻PTEN⁻ cells. (b, c) Expressions of IL6 and SOCS3 are analyzed by RT-PCR in p53⁻PTEN⁻ and p53⁻PTEN⁻SOCS3⁺ cells. (d) Production of IL6 is analyzed by ELISA in p53⁻PTEN⁻ and p53⁻PTEN⁻SOCS3⁺ cells. (e) MCF10Ap53⁻PTEN⁻ and MCF10Ap53⁻PTEN⁻SOCS3⁺ implanted in the mammary fat pad of NOD/SCID mice and monitored over 8 weeks. (f) MCF10Ap53⁻PTEN⁻ and MCF10Ap53⁻PTEN⁻SOCS3⁺ tumor weights are presented in bar graphs and representative macroscopic tumor pictures are in insert. (g) Human IL6 levels in mice bearing MCF10Ap53⁻PTEN⁻ or MCF10Ap53⁻PTEN⁻SOCS3⁺ tumors as well as in mice without tumor were measured by ELISA. (h) Mice with MCF10Ap53⁻PTEN⁻ tumors were treated with tocilizumab and docetaxel and tumor growth was monitored during the course of 8 weeks.