AQP1 Expression In Non-small Cell Lung Cancer And Its Mechanism To Promote The Development Of Lung Adenocarcinoma

BackgroundLung cancer is a malignant tumor which has the highest morbidity and mortality in China and the whole world in recent years, following changed life mode and worsen environment. The incidence and mortality rates of lung cancer are still rising, which has already become the first cancer killer for human health. Although great progress in the treatment of lung cancer in recent years, the quality of life of patients with lung cancer and the overall survival rate are not ideal with poor therapeutic effect and poor prognosis because of the higher degree malignancy and more difficult early diagnosis leading patients with advanced or distant metastatic lung cancer when they are diagnosed. Aquaporin 1(AQP1), as a specific channel, to quickly transport the water molecules across the plasma membrane, plays a very important role in the occurrence and development of tumors. Therefore, it is very important for finding a new method of cancer prevention to explore and study the mechanism of tumor genesis. PurposeThe purpose of this research is to observe AQP1 specific expression in non-small cell lung cancer(NSCLC), tumor growth and the changes in glucose metabolism, explore the mechanism of AQP 1 promoting the cancer development, and provide a new way for cancer treatment. MethodsIn this study, Firstly, Immunohistochemical technology is used to detect AQP1 expression in 64 NSCLC and 32 adjacent tissues, then analyze the correlation between AQP1 expression and lung adenocarcinoma progression. Secondly, we established urethane-induced mouse lung adenocarcinoma model and verified the correlation between AQP1 expression and lung adenocarcinoma progression. Finally, we use acetazolamide(AQP1 inhibitors), metformin(glycolysis to enhance promoter), 2-fluorodeoxyglucose(2-DG, glycolysis inhibitors) to treat mice with lung adenocarcinoma induced by urethane, and observe the number of nodules on lung surface. Further, immunohistochemistry and Western blot were used to detect AQP1 expression in lung tissue. The kits were used to detect the levels of lactic acid and pyruvic in lung cancer tissue. Results1. The positive rate of AQP1 expression in the tissue adjacent to carcinoma was 15.63%(5/32), whereas it was 63.64%(28/44) in lung adenocarcinoma and was negative expression in lung squamous carcinoma tissue.2. The expression of AQP1 in lung adenocarcinoma was statistically significant with tumor differentiation degree and lymph node metastasis(P< 0.05), but had no statistically significant with clinical factors such as age, gender, tumor stage(P > 0.05).3. In urethane-induced mouse lung cancer model, the correlation analysis between AQP1 expression in lung adenocarcinoma and cancer confirmed clinical results. Acetazolamide could down regulate AQP1 expression in mice, reduced pulmonary nodule numbers, inhibit tumor growth, at the same time, reduce the lactic acid content in the lung tissue(P < 0.05), indicating inhibiting glycolysis level in mice.4. Metformin could promote glycolysis, elevate lactate and pyruvic content in the lung tissue, increase lung nodule numbers, and raise the AQP1 expression in lung tissue(P < 0.05), whereas 2- deoxyglucose glucose could inhibit glycolysis in mice, reduce the lactate and pyruvic content in the lung tissue, decrease the lung nodule number and the AQP1 expression in lung tissue(P < 0.05). Conclusions1. AQP1 is highly expressed in lung adenocarcinoma tissues and can be used as a pathologic diagnosis and therapeutic target for lung adenocarcinoma.2. AQP1 expression in lung adenocarcinoma was associated with tumor differentiation degree and lymph node metastasis, but had no obvious correlation with clinical factors such as age, gender, tumor stage.3. The mechanism of AQP1 promoting tumor growth is related to glycolysis re-programming.4. AQP1 inhibition or glycolysis prevention may be an effective measure for prevention and treatment of lung adenocarcinoma.