Abstract:

Objective To explore the mechanism of lipid metabolism disorder promoting the progress of lung cancer based on the oxidized low density lipoprotein （ox?LDL）/ human lectin?like oxidized low density lipoprotein receptor 1（LOX?1） signaling pathway. Methods Eighty?one identified lung adenocarcinoma tissues with paired adjacent non?cancerous tissues （at least 5 cm away from the tumor） were collected from our hospital， and the expression of LOX?1 was detected by immunohistochemistry. LOX?1 was overexpressed in lung adenocarcinoma cell lines （A549 and H1299 cells）. Cell invasion ability was measured by Transwell. Cells were treated with different concentrations of oxLDL， and cellular LOX?1 expression was investigated. Results LOX?1 staining in the tumor was significantly stronger than that in the non?cancerous tissue samples （99.4 vs. 16.2 for median H score， P < 0.001）. High LOX?1 expression was significantly correlated with low survival （P < 0.001）. As compared with the patients without lymph node metastasis， those with lymph node metastasis had higher LOX?1 level （83.2 vs. 121.1 for median H score， P < 0.01）. Overexpression of LOX?1 in lung cancer cells significantly promoted the number of invasive and metastatic cells （P < 0.01）. In addition， LOX?1 was an essential functional target for oxLDL?induced metastasis of lung cancer cells. Itatinib inhibited the metastasis of LOX?1 overexpressed A549 in vitro. Conclusions With an increase in oxLDL level， the expression of LOX?1 increases. Up?regulation of LOX?1 promotes metastasis of lung cancer， and its mechanism may be related to activation of the JAK1/STAT6 signaling pathway.

Key words: oxidized low density lipoprotein, human lectin?like oxidized low density lipoprotein receptor 1, lung cancer, lipid metabolism