Exogenous High‐Mobility Group Box 1 Inhibits Apoptosis and Promotes the Proliferation of Lewis Cells via RAGE / TLR 4‐Dependent Signal Pathways

Upregulated high‐mobility group box 1 ( HMGB 1) has been found in many diseases. Nevertheless, the function of HMGB 1 on modulating the proliferation of lung cancer cells (Lewis cells) and inhibiting apoptosis is poorly understood, as well as the involved intracellular signalling. In the present study, we firstly found the apoptosis of Lewis was increased following Hanks’ balanced salt solution ( HBSS )‐induced starvation, while it was rescued after exogenous HMGB 1 protein was added; furthermore, the receptor for advanced glycation end products ( RAGE ) and T oll‐like receptor ( TLR 4) could coordinately improve the proliferation of tumour cells in vitro, and HMGB 1 could enhance the phosphorylation of PI 3 K / A kt and E rk1/2, inhibit the expression of pro‐apoptosis protein B ax and promote the expression of anti‐apoptosis protein B cl‐2. These findings clearly demonstrated that HMGB 1– RAGE / TLR 4‐ PI 3 K ‐ A kt/ E rk1/2 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.