Targeting IRS-1/mPGES-1/NOX2 to inhibit the inflammatory response caused by insulin-like growth factor-I-induced activation of NF-κB and NLRP3 in cancer cells.

Abstract

The levels of insulin-like growth factor-l (IGF-1) and reactive oxygen species (ROS) are abnormally elevated in various tumour tissues, and IGF-1 has been reported to be associated with the development and progression of inflammation in cancers. In this study, we found that IGF-1 activated nuclear factor-κB (NF-κB) and NLRP3 inflammatory signalling via IRS-1/mPGES-1/NOX2-regulated ROS. Additionally, in the B16-F10 tumour-bearing mouse model, the number of tumours, tumour growth, invasion of tissues and expression of proinflammatory factors in peripheral blood were significantly decreased by treatment with an inhibitor combination compared with those of the IGF-1 group. Taken together, targeting IRS-1/mPGES-1/NOX2 to inhibit inflammation related to NF-κB and NLRP3 is a potential strategy for controlling the development and progression of cancer.