The Lung Injury Mechanism Of Iron Overload And Its Pro-carcinogenic Efficacy For Lung

Lung cancer is currently one of the largest common malignant tumors that harms human health and threatens human life in the world. In recent years, the pressure and challenges keep increasing in the current clinical treatment of lung cancer due to China's growing aging population, people unhealthy lifestyle and environmental pollution, andthe increase of lung cancer incidence and mortality year by year. In theclinical work, it shows that many lung cancer patients exhibit abnormal phenomenon of iron metabolism, which is also approved in the relevant literature reports. Therefore, aim of this study is to investigate how iron overload affects the abnormalities of lung cancer, and ultimately it can provide realistic potential or theoretical basis for the treatment of lung cancer.The investigations are going to start from cells then to tissues and ultimately to animals.In vitro experiments, the MTT method was utilized to test the effects of different concentrations of iron dextran,and Iron chelator deferoxamine on proliferation in human lung cancer A549 cells; DCF-DA method was used to detect ROS level,cell scratch was used to determine cell migration. In vivo experiments, the mouse lewis lung carcinoma subcutaneous model and urethane-induced mouse lung cancer model were used to evaluate the role of iron dextran in the development of lung cancer.Tumor weight and increased volume were monitored. to evaluate tumor development, autonomic activities, body weight and body surface temperature were monitored. to evaluate life quality. HE staining was used to evaluate lung pathology the changes in ROS,TIBC, T-AOC, Fn, MDA,IL-6,IL-8, TNF?,VEGF and other content mice serum were examined by the ELISA kit. In addition, western blot was used to test relevant protein such as HO-1 and iNOS. Protein expression of HIF-1? ? INOS ? HO-1and COX2 in mouse lung was detected by immunohistochemistry to explore the relationship between iron dextran and lung cancer.In vitro experiments showed that: 1) iron dextran could promote proliferation and facilitate cell growth in a dose-dependent manner in A549 cells; 2) DFO was able to inhibit the increased cell proliferation and apoptosis. 3) Iron dextran significantly increased intracellular ROS levels in a dose-dependent manner in A549 cells. 4) Dextran iron can promote the migration of tumor cells. In vivo results showed that iron dextran could 1) promote tumor growth; 2) reduce the life quality of mice with tumor; 3) reduce the lifespan; 4) increase the levels of serum Fn,ROS,TIBC,IL-6,IL-8, TNF?,VEGF,MDA. 5) decrease the content of T-AOC. Western blot results showed that protein expression(HO-1 and INOS) was significantly higher in iron dextran group compared to the model. HE pathological results showed that iron dextran could significantly increase lung injury in mice with lung cancer.. Immunohistochemistry showed that iron dextran increased the color density of HO-1, HIF-1?, COX2, INOS in mouse lung tissue with cancer.In summary, the iron overload caused by iron dextran provided favorable conditions for tumor development, and therefore aggravated lung cancer. This aspect prompted us to pay attention to the control of iron in the clinical treatment of lung cancer.