摘要
目的探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)组织中锰超氧化物歧化酶(manganese superoxide dismutase,Mn SOD)、去乙酰化酶3(sirtuin 3,SIRT3)的表达,以及两者与NSCLC生物学特征的关系。方法采用免疫组化及Western blot法检测89例NSCLC及对应癌旁(直径≥10 cm)肺组织中Mn SOD、SIRT3蛋白的表达,探讨与NSCLC组织类型、TNM分期、分化程度、淋巴结转移的相关性。结果免疫组化及Western blot结果显示:与癌旁肺组织相比,Mn SOD、SIRT3蛋白在NSCLC中的表达明显降低;免疫组化图像分析结果显示癌旁组织中Mn SOD、SIRT3蛋白含量平均光密度值(OD值)为(0.428±0.031)、(0.403±0.035),而NSCLC组织中Mn SOD、SIRT3蛋白OD值显著降低,且两者表达与NSCLC分化程度、肿瘤T分期呈正相关(P<0.05,P<0.01);而与病理类型及有无淋巴结转移无相关性(P>0.05)。结论 NSCLC组织中MnSOD、SIRT3蛋白表达降低,两者联合检查可能对预测肿瘤的恶性程度有一定的意义。
Purpose To investigate the expression of manganese superoxide dismutase( Mn SOD) and sirtuin 3( SIRT3)in non-small cell lung cancer( NSCLC) and their relationships with tumor biological characteristics. Methods The expression of Mn SOD and SIRT3 proteins in surgical specimens of 89 NSCLC and adjacent tissue of carcinoma( ≥10 cm) were detected by immuno-histochemical method and Western blot. The relationship between types of tumor tissue,TNM stages,differentiation and lymph node metastasis were also analyzed. Results Immunohistochemistry and Western blot showed that the expression of Mn SOD and SIRT3 protein in NSCLC were significantly decreased compared with the adjacent tissues, Immunohistochemical images showed that the average optical density value( OD value) of Mn SOD and SIRT3 protein in the adjacent tissues of cancer was( 0. 428 ± 0. 031) and( 0. 403 ± 0. 035),while the OD values in the NSCLC tissues decreased significantly. And the levels of expression of Mn SOD and SIRT3 protein were positively correlated with the differentiation and stages of the tumor( P < 0. 05,P < 0. 01),but there were no significant correlation with the pathological types and lymph node metastasis( P > 0. 05). Conclusion The expression of Mn SOD and SIRT3 protein in NSCLC decrease,and the expression of these proteins may have implications for predicting malignancy of the tumor.
引文
[1]Zhang F,Duan S,Tsai Y,et al.Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer[J].Cancer Sci,2016,107(6):746-754.
[2]Ganini D,Petrovich R M,Edwards L L,et al.Iron incorporation into Mn SOD A(bacterial Mn-dependent superoxide dismutase)leads to the formation of a peroxidase/catalase implicated in oxidative damage to bacteria[J].Biochim Biophys Acta,2015,1850(9):1795-1805.
[3]Ansari A,Rahman M S,Saha S K,et al.Function of the SIRT3mitochondrial deacetylase in cellular physiology,cancer,and neurodegenerative disease[J].Aging Cell,2017,16(1):4-16.
[4]Margaret A L,Syahruddin E,Wanandi S I.Low activity of manganese superoxide dismutase(Mn SOD)in blood of lung cancer patients with smoking history:relationship to oxidative stress[J].Asian Pac J Cancer Prev,2011,12(11):3049-3053.
[5]Tarhini A A,Belani C P,Luketich J D,et al.A phase I study of concurrent chemotherapy(paclitaxel and carboplatin)and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer[J].Hum Gene Ther,2011,22(3):336-342.
[6]Zou X,Santa-Maria C A,O’Brien J,et al.Manganese superoxide dismutase acetylation and dysregulation,due to loss of SIRT3activity,promote a luminal B-like breast carcinogenic-permissive phenotype[J].Antioxid Redox Signal,2016,25(6):326-336.
[7]韩义明,饶兰,丁莉,等.非小细胞肺癌中BRAF V600、EGFR基因突变与临床病理特征的关系[J].临床与实验病理学杂志,2017,33(4):375-378.
[8]Loo S Y,Hirpara J L,Pandey V,et al.Manganese superoxide dismutase expression regulates the switch between an epithelial and a mesenchymal-like phenotype in breast carcinoma[J].Antioxid Redox Signal,2016,25(6):283-299.
[9]Adachi T,Kano A,Nonomura S,et al.Histone deacetylase inhibitors stimulate the susceptibility of A549 cells to a plasma-activated medium treatment[J].Arch Biochem Biophys,2016,606:120-127.
[10]Zhang J,Song X,Cao W,et al.Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol[J].Sci Rep,2016,6:32928.