报道指出，Resistin 和细胞因子信号抑制因子（Suppressor of Cytokine Signaling, SOCS）对前列腺癌（PCa）细胞的增殖和存活具有调节作用。目前尚不清楚 SOCS 分子中是否有任何介导 Resistin 对 PCa 细胞的促有丝分裂效应的分子。我们使用 PC-3 人类PCa 细胞，发现 Resistin 呈剂量和时间依赖方式上调表达 SOCS3 和 SOCS5 mRNA，而不是 SOCS7 mRNA。具体抑制 TLR4、ERK、p38 MAPK、JNK、PI3K 和 JAK2 特异性抑制剂预处理可以阻止 Resistin 引起的 SOCS3 和 SOCS5 表达增加及细胞增殖。然而，TLR2 抑制剂预处理对 Resistin 介导的 SOCS3 和 SOCS5 表达没有影响。此外，Resistin 对 SOCS3、SOCS5 和 SOCS7 mRNA 水平的影响具有细胞类型特异性。过度表达 SOCS3 或 SOCS5 进一步增强 Resistin 刺激的 PC-3 细胞生长，而沉默 SOCS3 或 SOCS5 反对 Resistin 增加的细胞生长。进一步的 PCa 组织分析表明，癌组织中 RETN、TLR4、SOCS3 和 SOCS5 mRNA 水平较良性前列腺增生高，并且 RETN、TLR4 和 SOCS5 之间呈正相关。这些数据表明 SOCS5、TLR4 和在较小程度上是 SOCS3 调节 Resistin 对 PC-3 PCa 细胞的有丝分裂刺激效应。

Resistin and suppressors of cytokine signaling (SOCSs) have been reported to regulate prostate cancer (PCa) cell proliferation and survival, respectively. Whether any of the SOCS molecules mediate the mitogenic effect of resistin on PCa cells is unknown. Using PC-3 human PCa cells, we found that resistin upregulates the expression of SOCS3 and SOCS5 mRNA, but not SOCS7 mRNA, in a dose- and time-dependent manner. The resistin-induced increases in SOCS3 and SOCS5 expression and cell proliferation were prevented by pretreatment with specific inhibitors of the TLR4, ERK, p38 MAPK, JNK, PI3K, and JAK2 proteins. However, pretreatment with a TLR2 inhibitor had no effect on resistin-mediated SOCS3 and SOCS5 expression. In addition, the effects of resistin on SOCS3, SOCS5, and SOCS7 mRNA levels were cell type-specific. Overexpression of either SOCS3 or SOCS5 enhanced further resistin-stimulated growth of PC-3 cells, whereas silencing SOCS3 or SOCS5 antagonized resistin-increased cell growth. Further PCa tissue analysis demonstrated higher levels of RETN, TLR4, SOCS3, and SOCS5 mRNAs in cancer tissues than benign prostate hyperplasia and indicated positive correlations among RETN, TLR4, and SOCS5. These data suggest that SOCS5, TLR4, and, to a lesser extent, SOCS3 can mediate the mitogenic effect of resistin on PC-3 PCa cells.