Fig.

IL-6 mediated drug resistance in RCC cells. Following anti-RCC drug stimulation, IL-6 is secreted by RCC cells. It then binds IL-6 receptor and results in activation of the JAK/STAT3 signaling pathway, leading to the transcription of STAT3 target genes, i.e. VEGF or SOCS3. SOCS3 suppresses STAT1 activation. STAT3 and NF-κB interact at multiple levels, and promote inflammation, increasing tumor cell proliferation and survival as well as tumor angiogenesis and metastasis²⁷⁾. IL-6 can also activate the AKT/mTOR pathways.