Expression And Significance Of MnSOD,SIRT3 Proteins In Non-small Cell Lung Cancer

BackgroundNon-small cell lung cancer?NSCLC?is a common malignant tumor in the respiratory system,which its therapeutic method including surgical resection,radiotherapy,chemotherapy and targeted therapy.So far,the regulatory mechanism of the occurrence and development of NSCLC has not been clarified,the early clinical symptoms of patients are not specific,and the prognosis is poor.Most solid tumors in the body are short of blood supply due to the rapid growth and lack of blood supply in the body.Similarly,there are also cases of ischemia,hypoxia,abnormal metabolism and inflammatory reaction in NSCLC tumors.Endogenous factors such as inflammatory stimulation will cause reactive oxygen species?ROS?released in the body.ROS and oxidative stress will lead to imbalance of oxidation-antioxidant capacity of the body,increase lipid peroxidation,increase tumor susceptibility and angiogenesis in cells,and cause gene mutation in cells,leading to increase DNA damage and further gene recombination and cell malignancy.Hypoxic environment changes tumor cell metabolism,and mitochondrial respiratory chain dysfunction reduces the aerobic oxidation efficiency of tumor cells,leading to the continuous formation of ROS in tumor cells'mitochondria,promoting the continued oxidation of mitochondrial proteins and the breakdown of mitochondrial function,and the continuous production of ROS.Therefore,ROS produced continuously in the hypoxic environment causes oxidative stress and promotes the malignant proliferation and invasion and metastasis of tumors.Then,under the hypoxic environment,the further mechanism of ROS promoting metastasis of NSCLC tumor cells needs to be further clarified.The microenvironment of hypoxia and antioxidant system in NSCLC tumor tissues affects drug sensitivity.Under normal circumstances,the physiological level of ROS in cell proliferation,cell differentiation and other biological role in signal transduction,maintain intracellular ROS generation and the dynamic balance between ROS removal,manganese superoxide dismutase?MnSOD?,also called SOD2,is a major way the body remove mitochondrial ROS,MnSOD convert super oxygen anion and other intracellular ROS to H₂O₂ and cleared.In recent years,the family of sirtuins?SIRTs?has played a significant role in energy metabolism,oxidative stress,gene repair and anti-tumor activities.Studies have pointed out that SIRT3 is the only has to acetylation enzyme activity SIRTs,SIRT3 on histone/histone acetylation,adjust the energy metabolism of mitochondria,improve the level of ATP in the cell,thus protecting cells,give play to the role of anti-oxidation stress,reduce the apoptosis,SIRT3 caused mainly by MnSOD 122 lysine residues acetylation and thus activate MnSOD,reduce mitochondrial ROS generation in the cell,participate in anti-aging and anti-tumor effect.Therefore,SIRT3 may play an important role in the pathogenesis of tumor as an intermediary of energy receptors and ROS scavenging.However,no research has confirmed that in NSCLC,under hypoxic conditions,the oxidative stress of tumor is related to MnSOD-SIRT3.ObjectiveTo investigate the relationship between biological characteristics and pathological morphology of NSCLC,to observe the expression of MnSOD and deacetylase 3?Sirtuin 3,SIRT3?in NSCLC tissues,and to study the relationship between the expression of MnSOD-SIRT3 and the biological characteristics of NSCLC.Methods?1?The histological morphological structure of NSCLC was observed by hematoxylin eosin?HE?staining in 89 cases of recent surgery.?2?The expression of MnSOD protein and SIRT3 protein in 89 patients with NSCLC and lung tissuesadjacent to cancer?>10cm?wasdetected by immunohistochemistry SP method.?3?Western blot and semi-quantitative analysis of MnSOD protein and SIRT3 protein expressions in 89 patients with NSCLC and adjacent tissues.Results?1?HE staining showed that the histological type of 89 cases of lung cancer was NSCLC,and the clinical pathology included squamous cell carcinoma?51cases?and adenocarcinoma?38 cases?.Pathology classification,I grade,34cases,II grade,25 cases,III grade,30 cases;Tumor stage,T1-2 stage,62cases,T3 stage,27 cases;Lymph node staging,N0 phase,36 cases,N1-2phase,53 cases.?2?Immunohistochemical staining showed that MnSOD protein and SIRT3 protein were positively expressed in the cell membrane and cytoplasm of NSCLC and lung tissues adjacent to NSCLC,98.88%of patients were positive in MnSOD expression,96.63%of patients were positive in SIRT3expression,significantly higher than in tumor tissues of NSCLC patients MnSOD?70.79%?and SIRT3?67.42%?.?3?The expressions of MnSOD protein and SIRT3 protein in NSCLC were significantly decreased,and the two proteins were positively correlated with the differentiation degree of NSCLC and tumor T staging?P<0.05?.There was no correlation with pathological type?squamous cell carcinoma,adenocarcinoma?and lymph node metastasis?P>0.05?.?4?Semi-quantitative analysis by Western blot further showed that MnSOD protein and SIRT3 protein expressions in NSCLC decreased significantly compared with normal lung tissue adjacent to cancer,and decreased with the decrease of differentiation degree of NSCLC.ConclusionNSCLC mainly includes the histological types of squamous cell carcinoma and adenocarcinoma in this group,and the decrease of MnSOD protein and SIRT3protein in the tissues of NSCLC may be positively correlated with the differentiation degree of NSCLC and tumor T stage.A combination of the two tests may be useful in predicting the degree of malignancy of tumors.