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Study On Expression Of Ferroportin1in Non-small Cell Lung Cancer And Its Effect On Lung Cancer Cells Growth And Proliferation

Posted on:2015-03-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:J F LinFull Text:PDF
GTID:1224330434952033Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Objective: Lung cancer is currently a kind of malignant tumor with the highest incidence and mortality in the world. Lung cancer is mainly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for the majority of primary lung cancer. Many studies have shown that iron overload is one of the important causes to promote cell malignant transformation and eventual development to malignant tumors. Ferroportin1is currently the only known exportin of non-heme iron on the cell surface and also the sole receptor of hepcidin, mainly responsible for intracellular iron export. It is thereby an important part of the systemic iron metabolism. Hepcidin binding to ferroportin1on the cell membrane induces its internalization and degradation, resulting in cellular iron retention and decreased iron export. This thereby provides favorable conditions for cell carcinogenesis. In this study, the expression level of ferroportin1in non-small cell lung cancer tissue specimens is detected, and its relationship with pathological features is analyzed. The relationship between ferroportin1and lung cancer cell growth is further analyzed by in vitro cell biology experiments. And the mechanism of action of ferroportin1in lung cancer cell proliferation and growth was preliminarily analyzed.Methods:(1) The localization and expression of ferroportin1in42cases of NSCLC tissue specimens and23cases of normal lung tissue specimens were detected by immunohistochemistry (IHC), and its relationship with pathological characteristics and clinical staging were analyzed.(2) The expression of ferroportin1in various NSCLC cell lines was detected by Western-blot method, and the cell line with the most significant reduction in ferroportin1was screened out. The eukaryotic expression vector of ferroportin1was constructed to promote ferroportin1overexpressed in the target tumor cells. The effect of elevated expression level of ferroportin1on cancer cell proliferation and growth was studied by using WST-8test and cell colony formation experiments.Results:(1) The expression level of ferroportin1in non-small cell lung cancer tissues was significantly reduced compared with normal lung tissues. The differences the expression level of ferroportin1in squamous cell carcinoma and adenocarcinoma were not statistically significant; and the differences in different clinical staging were also not statistically significant.(2) The expression levels of ferroportin1in non-small cell lung cancer cells were reduced in different degrees compared with bronchial epithelial cells, in which H520showed the most significant reduction. The elevated expression of artificially transfected ferroportin1 inhibited H520cell proliferation.Conclusion:The expression level of ferroportin1was reduced in non-small cell lung cancer tissues, which was not correlated to pathological characteristics and clinical staging. The in vitro experiments confirmed that ferroportin1could inhibit H520lung cancer cell growth and proliferation, indicating that the hepcidin-ferroportin systems and iron balance disorders played important roles in the occurrence and development of cancer.
Keywords/Search Tags:ferroportin1, non-small-cell lung cancer, hepcidin, cell proliferation, iron metabolism
PDF Full Text Request
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