Detection Of Serum Fe And Ferritin Levels In Patients With Non-small Cell Lung Cancer And Study On The Anti-tumor Effects Of Iron Chelator

Background and purpose: Lung cancer is the first cancer incidence in China.About80% of lung cancer are non-small cell lung cancer(NSCLC),and most of them have been diagnosed with advanced tumors due to their highly invasive nature.At present,the comprehensive mode of surgical radiotherapy and chemotherapy and targeted therapy for non-small cell lung cancer has a poor prognosis.The search for an effective treatment for NSCLC remains the goal at this stage.Iron is an essential nutrient for cell DNA synthesis.Studies have shown that cancer cells are more dependent on iron than normal cells,making them more sensitive to iron deficiency than normal cells.This study analyzed the correlation between serum Fe and ferritin in iron metabolism indexes and TNM staging in patients with non-small cell lung cancer,and also studied the anti-tumor effect and mechanism of iron chelator deferoxamine in non-small cell lung cancer,so as to provide reference for seeking new treatment methods for non-small cell lung cancer.Material and methods: The medical records and blood samples of 47 patients with non-small cell lung cancer and 41 patients with pneumonia were collected to detect the level of iron metabolism indexes(serum iron,ferritin,transferrin,sTfR,unsaturated iron binding capacity,Total iron binding capacity),analyze the differences of iron metabolism indexes between patients with non-small cell lung cancer and patients withpneumonia,and further analyze their correlation with TNM staging of non-small cell lung cancer.In the basic experiment,the lung adenocarcinoma H1975 cells were treated with iron chelator deferoxamine,and the proliferation inhibition effect of different concentrations of deferrosamine on H1975 cells was detected by MTT assay.Flow cytometry was used to detect the apoptosis rate.Western blot was used to detect the expression of apoptosis proteins caspase-3,cleaved caspase-3,cleaved caspase-9,Bax,Bcl-2,Bcl-xl,pathway related proteins CHOP,Bip,ATF-4,ATF-6,XBP-1s,p-eIF2?,p-PERK.To further analyze the inhibitory effect of deferoxamine on the growth of transplanted H1975 cell immunodeficiency mice.Results: Serum iron(28.30 ± 9.01)?mol/L in non-small cell lung cancer group was higher than that in pneumonia group(23.55±9.31)?mol/L,P<0.05.Ferritin(288.70±145.90)?g/L in non-small cell lung cancer group was higher than that in pneumonia group(214.20±107.70)?g/L,P<0.05.In the non-small cell lung cancer group,serum ferritin and ferritin levels were correlated with tumor TNM stage(P<0.05),while ferritin levels were significantly correlated with tumor TNM stage(P<0.01).The results of basic experiments showed that the antiproliferative effect of DFO on H1975 cells.It can induce apoptosis of H1975 cells,accompanied by down-regulation of bcl-2,bcl-xl,caspase-3,and up-regulation of Bax,cleaved caspase-3,and cleaved caspase-9.During the induction of apoptosis in H1975 cells,deferramine activates the caspase-dependent mitochondrial pathway.The expression of ER stress related proteins CHOP,Bip,ATF-6,XBP-1s,p-PERK and p-eIF2? is up-regulated.Meanwhile,ROS accumulation is detected by flow analysis.Deferoxamine inhibited the growth of H1975 cell immunodeficiency mouse xenograft tumors.Conclusions: Patients with non-small cell lung cancer had higher iron load than thosewith pneumonia,and serum iron and ferritin were correlated with TNM stage of non-small cell lung cancer.Iron chelating agent deferoxamine can promote apoptosis of lung adenocarcinoma cells through ROS-dependent ER stress and stereotactic dysfunction.So iron chelation may be a potential treatment for non-small cell lung cancer.