Expression And Function Of NGAL Gene In Lung Cancer

【Background】Lung cancer, also known as primary bronchial lung cancer, is one of the highest morbidity and mortality of malignant tumors. The morbidity of lung cancer presents rising and young tend, and the mortilaty rate ranks first of all kinds of cancer in China. There are two types of lung cancer according to the pathological type: small cell lung cancer and non-small cell lung cancer. Small cell lung cancer accounts for 25% of the total number of lung cancer, and Non-small cell lung cancer accounts for 75% of the total number of lung cancer, which contains squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. Small cell lung cancer, which accounts for about 13% of newly diagnosed lung cancer, is a kind of rapid growth, early stage invas ive disease, lymph node and distant metastasis, sensitive to the chemotherapy, as well small cell lung cancer is about 1/3 for limited stage, chemotherapy and radiotherapy can obtain an objective response rate of about 80%, 2/3 for an extended period of time, prognosis the poor, the median survival time was 10 months. The standard treatment for non-small cell lung cancer includes operation, radiotherapy, chemotherapy and other multiple treatments. Systemic therapy is one of the basic elements of multi modality therapy for non-small cell lung cancer. However, the vast majority of non-small cell lung cancer treatments are locally advanced and the cure rate is low. Since the early symptoms are often nonspecific, early diagnosis is difficult. Lung cancer patients are often check up with tumor metastasis and lost the chance of operation. For a malignant tumor, the primary causes of progression are infiltration and metastasis, which is the procedure of multi-stages, polygenes participation and adjustment of multifarious transcription factors, and involve in a series of patho-physiological responses. Studying the mechanism and etiology of lung cancer has an important clinical significance. NGAL(neutrophil gelatinase-associated lipocalin), as a new member of lipocalin family, was abnomally expressed in a lot of diseases and can form compounds with MMP-9 to play its function. Recently lots of studies show,NGAL protein overexpresses in some of tumor cells, and involved in poor differentiation and invas ion of cancer cells, but the expression and regulation mechanism of NGAL gene is still unclear.【Objective】 To verify the correlation between expression of neutrophil gelatinase-assoeiated lipocalin(NGAL) and the different differentiations of human lung cancer and to study the mechanism of growth, migration and invasion involved in NGAL in A549 cancer cells.【Methods】 Expression of NGAL was detected by immunochemistry in human lung cancer tissues and the tissues around edge of the cancer. Expression of NGAL in A549 cancer cells was observed by qPCR and Western-blot. Abilities of invasion and metastasis were evaluated by transwell invas ion and migration assay, and cell scratch assay in vitro. Protein expression of E-cadherin, Vimentin was measured by immunofluoresence and western blot. Expression of MMP-2 and MMP-9 were tested by western blot after lung cancer cells were treated by NGAL SiRNA. 【Results】 Positive expression rate of NGAL was 76.32%(58/76) in the lung cancer tissues, 13.3%(4/30) in adjacent tissues by immunochemistry. NGAL expression level in the lung cancer tissues were significantly higher than that in adjacent tissues. The rate of migration and invas ion in NGAL-siRNA group was(60.4±6.4)% compared to(50.5±4.4)% in the control group, there was a significant difference(p<0.05). Vimentin expression was suppressed, and E-cadherin was upregulated when NGAL was inhibited. MMP-2 and MMP-9 expression decreased when NGAL was knocked down. 【Conclusions】 The expression level of NGAL is highly expressed in lung cancer. NGAL may be one of important indicators involved in lung cancer infiltrated and transferred. NGAL might be one of potential targets for lung cancer treatment.