The Role Of CFTR In Cell Proliferation, Migration And Apoptosis Of Lung Adenocarcinoma

Lung cancer is one of the most common malignant tumors in the world with avery high mortality rate. The main two categories of lung cancer exist and these arenon-small and small cell lung carcinoma of which non-small cell carcinomacontributes to80percent of the total number of lung cancer cases. Lungadenocarcinoma is32-40percent of all the non-small cell lung cancer types and istherefore one of the main types of lung cancer. At present, the main methods for lungcancer treatment are surgery, chemotherapy, radiotherapy and biological therapy.Surgical treatment is the best choice in the early stages of lung adenocarcinoma. Theearly common symptoms of patients with lung adenocarcinoma include fever andbreathing difficulties which can be ignored easily. This means patients with lungadenocarcinoma often miss the best opportunity of treatment. At present, somepatients with late stage lung cancer have benefitted from immune therapy which canbe identified on a molecular basis among individuals. This method does not have theside effects similar to chemotherapy drugs or the killing of both normal and cancercells which is a common phenomenon during radiotherapy treatment. Hence, it istherefore meaningful to research and screen for potential effective therapeutic targets.In the literature it has been found that the mutation of CFTR gene may increase orreduce the risk of certain cancers. Since the processes of proliferation, migration andapoptosis are included in tumour development, therefore, we investigated the role ofCFTR in lung adenocarcinoma cell proliferation, migration and apoptosis.Methods: Both in vivo and in vitro experiment were included in this research.In vivo: Lung adenocarcinoma tissues were collected from the tumor hospital ofJilin Province, conventional paraffin embedding, sectioning (5μm) and then didimmunohistochemistry and TUNEL.In vitro: calu-3were cultured by conventional method, the CFTR activator(Genistein) and CFTR inhibitor (CFTRinh-172) were added to the cell. The optimal drug concentrations were determined by MTT and CCK-8method, that were thegroups of CFTR activator and CFTR inhibitor. We detected the CFTR proteinexpression, cell migration, cell apoptosis by immunofluorescence assay, scratch test,Hoechst33342staining, flow cytometry.Results: The result of immunohistochemistry: the expression of CFTR inwell-differentiated lung adenocarcinoma cells was higher than that in poorlydifferentiated lung adenocarcinoma cancer cells; the result of TUNEL,the tumor cellapoptosis rate of well-differentiated lung adenocarcinoma tissue was0.2316±0.0133,and the tumor cell apoptosis rate of poorly-differentiated lung adenocarcinoma tissuewas0.1175±0.0611.The optimal concentrations of Genistein were12.5μM、25μM、50μM/48h thatwere determined by MTT, The optimal concentrations of CFTRinh-172were5μM,10μM,20μM/48h that were determined by CCK-8; moreover, Genistein inhibitedproliferation of Calu-3, and CFTRinh-172promoted proliferation of Calu-3.The testsof immunofluorescence showed that there was no significant difference between theexpression of CFTR of Genistein group (1.266±0.059) or CFTRinh172group(1.340±0.006) and the expression of CFTR of control group (1.292±0.058)(P=0.619>0.05，P=0.225>0.05). Scratch tests showed that there was significantdifference (P=0.000<0.01) between the number of cell migration of Genistein (25μM72h) group (90.53±4.06) and the number of cell migration of control group(72h)(244.1±18.38); and there was no significant difference (P=0.268>0.05) between thenumber of cell migration of CFTRinh-172(10μM48h) group(148.3±17.70) and thenumber of cell migration of control group (48h)(134.1±10.04).The results of Hoechst staining and flow cytometry showed the number of cellapoptosis and the rate of apoptosis of the Genistein group were higher than that in thecontrol group, and there were significant difference (P=0.000<0.01)(P=0.018<0.05).Conclusion:The expression of CFTR in well-differentiated lung adenocarcinomacells was higher than that in poorly-differentiated lung adenocarcinoma cells.Findings from this study show that CFTR is involved in the cell differentiation of lung tissue was higher than that in poorly-differentiated lung adenocarcinoma tissue, andthere was an association between the expression of CFTR and cell apoptosis rate oflung adenocarcinoma thereby showing the involvement of the CFTR in cell apoptosisof lung adenocarcinoma. Genistein inhibited the proliferation and migration of lungadenocarcinoma cells while promoting cell apoptosis of these cells by making theCFTR chloride ion channels open. It therefore means that the openness of CFTR caninhibit proliferation and migration of Calu-3cells thereby promoting their apoptosis.CFTRinh-172promoted the proliferation of lung adenocarcinoma cells by making theCFTR chloride ion channels close.