Exogenous high-mobility group box 1 inhibits apoptosis and promotes the proliferation of Lewis cells via rage/tlr4-dependent signal pathways

Abstract

Upregulated high-mobility group box 1 (HMGB1) has been found in many diseases. Nevertheless, the function of HMGB1 on modulating the proliferation of lung cancer cells (Lewis cells) and inhibiting apoptosis is poorly understood, as well as the involved intracellular signaling. In the resent study, we firstly found the apoptosis of Lewis was increased following Hanks’ balanced salt solution (HBSS)-induced starvation, while it was rescued after exogenous HMGB1 protein was added; furthermore, the receptor for advanced glycation end products (RAGE) and Toll-like receptor (TLR4) could coordinately improve the proliferation of tumour cells in vitro, and HMGB1 could enhance the phosphorylation of PI3K/Akt and Erk1/2, inhibit the expression of ro-apoptosis protein Bax and promote the expression of anti-apoptosis protein Bcl-2. These findings clearly demonstrated that HMGB1–RAGE/TLR4- PI3K-Akt/Erk1/2 pathway contributed to the proliferation of Lewis. Moreover, our observations provide experimental and theoretical basis for clinical biological therapy for cancers; it also may be a new target for intervention and treatment of lung cancer