The Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China; Department of Immunology & Laboratory Immunology, Jiangsu University, Zhenjiang, China.
Scand J Immunol. 2014 Jun;79(6):386-94. doi: 10.1111/sji.12174.
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 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 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 pro-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.
高迁移率族蛋白 B1（HMGB1）在许多疾病中都被发现上调。然而，HMGB1 调节肺癌细胞（Lewis 细胞）增殖和抑制细胞凋亡的功能以及涉及的细胞内信号通路仍不清楚。在本研究中，我们首先发现，Hanks 平衡盐溶液（HBSS）诱导饥饿后 Lewis 细胞的凋亡增加，而添加外源性 HMGB1 蛋白后则得到挽救；此外，晚期糖基化终产物受体（RAGE）和 Toll 样受体（TLR4）可以协同促进肿瘤细胞在体外的增殖，HMGB1 可以增强 PI3K/Akt 和 Erk1/2 的磷酸化，抑制促凋亡蛋白 Bax 的表达，促进抗凋亡蛋白 Bcl-2 的表达。这些发现清楚地表明，HMGB1-RAGE/TLR4-PI3K-Akt/Erk1/2 通路促进了 Lewis 的增殖。此外，我们的观察结果为癌症的临床生物治疗提供了实验和理论基础；它也可能成为干预和治疗肺癌的新靶点。
