Expression Of Carbonic Anhydrase â…¨ In NSCLC And Its Relationship With VEGF And Ki67

【Background】Lung cancer has already become the cardinal reason that majority of nations(include China ) cancers cause death in the world currently.According to the statistics, 2005, 429,000 people die in lung cancer in China, while this number will turn over in the next century.lung cancer is divided into two major types according to the clinical situation and the biology property in the world:The small cell lung cancer(small cell lung carcinoma, SCLC) and non-small cell lung cancer.(non-small cell lung carcinoma, NSCLC)。Among them, the non-small cell lung cancer is again divided into cardinal histology types such as squamous - cell carcinoma, adenocarcinoma and big cell cancer etc..Chemotherapy and Radiation therapy both are the cardinal means that the tumor treats, with the 3D proper form technique of evolve and expand, Radiation therapy is one of the important treatment methods that the treatment of lung cancer, the position benefit shows importance。NSCLC shares 85% of lung cancer, it has more malignant degree , often resist to Radiation therapy.Domestic and international research expresses that lacking the oxygen is one of the important reasons of resistance to Radiation therapy, how judge whether the tumor tissue existence lacks oxygen becomes the hot spot that the lung cancer studies currently, carbonic anhydraseⅨ( CAⅨ) is a new-found carbonic anhydrase household(CAs) different constructions ,which is a kind of new tumor antigen and have a latent function in the middle of regulating cell enzyme amplification and tumor formation, and contain closely related metabolism with hypoxia of tumor.CAⅨat the earliest stage was in 1993 discovered MN proteinase in the middle of uniting the HeLa cell of the person's temple cervicis cancer of development with human milk adenocarcinoma cell and fastenning by Pastorekova[2], 1994, Pastorek turned the cDNA of CAⅨto dye small rat through a genetic engineering of NIH 3 T3 cell , discovered cell enzyme amplification, the cell indirectly touched to repress disappearance, the cell period shortenned, the DNA petpide synthetase increased and erupted now that proteinase has the likeness of structure with carbonic anhydrase household(CAs) , and is confirmed for a kind of carbonic anhydrase household(CAs) isomerase,named after CAⅨ[3].Currently, outbreak rate and death rate of lung cancer have become the first of malignant tumor , the lung cancer treats in recent years and the member sign of prognosis becomes studying hot spot, the research of CAⅨorganizes a series of variety and evaluation that the tiny environment anoxia causes to undoubtedly have important meaning in the diagnosis of the lung cancer and the function of the under medical treatment to the understanding lung cancer.Currently CAⅨand the relativity research of the lung cancer less, especially the CAⅨstill have no related report way currently in the expression in the non-small cell lung cancer in later period.【Objective】this research test the express of CAⅨin hypoxia lung cancer cell and nomal lung cancer cell, analyze the relation of CAⅨthe expression and the lung cancer cell tiny environment lack the relativity of oxygen; carbonic anhydraseⅨ,VEGFand Ki67 protein were detected by immunohistochemical method in 76 cases of NSCLC and 10 cases of lung inflammatory pseudotumor. To investigate he expression of carbonic anhydraseⅨand its relationship with VEGF and Ki67 in NSCLC.;The first step inquiry into the functions of CAⅨin lung cancer Etiologic and treatment.【Methods】this research is mainly divided into two parts:1.Adopt Western-blot method's examination CAIX protein in hypoxia adenocarcinoma A549 and normal A549 cell, relatively lack oxygen appearance under and often under the oxygen appearance CAIX at person the adenocarcinoma A549 whether expression within cells exists difference;2.carbonic anhydraseⅨ,VEGFand Ki67 protein were detected by immunohistochemical method in 76 cases of NSCLC and 10 cases of lung inflammatory pseudotumor. (33 scale cancers, 43 adenocarcinomas) ,inquiry into CAⅨexpression in the non-small cell lung cancer(NSCLC) and its relation with curative effect of Radiation therapy, analyze its relation with VEGF and Ki67.【Result】1.Adopt Western-blot method's examination CAIX protein in hypoxia adenocarcinoma A549 and normal A549 cell,After developing after 24 hours the proteinase of CAⅨis in the normal cell set and hypoxia development, the cell set expresses to appear to show obvious difference with hypoxia cell, the set expresses to obviously increase Gao and express CAIX the proteinase and lung cancer cell lacks oxygen related, hint that the proteinase of CAⅨexpresses to be one of the important biology index signs that reflects lung cancer to hypoxia, therefore, pass can judge lung cancer cell tohypoxia appearance to the CAⅨproteinase examination.This research discovers that the proteinase of CAⅨis in the lung adenocarcinoma cell development set as usual and lacks an of oxygen development set and expresses existence difference, hypoxia and provides in the lung cancer for the further research basis.2.carbonic anhydraseⅨ,VEGF and Ki67 protein were detected by immunohistochemical method in 76 cases of NSCLC and 10 cases of lung inflammatory pseudotumor. (33 scale cancers, 43 adenocarcinomas) ,carbonic anhydraseⅨwas expressed in 45 of 64 cases of NSCLC and not expressed in benign tissue.VEGF was expressed in 55 of 76 cases and Ki67 was expressed in 32 of 76 cases The expression of carbonic anhydraseⅨin SC was higher than in AC(69.7% vs 27.9% P =0. 001).In 34 case who receive radiotherapy , The expression of carbonic anhydraseⅨis positively correlated with VEGF (r=0.231 P=0.043).The expression of carbonic anhydraseⅨin SD+PD group was higher than in CR+PR group ( 68.4% vs 33.3% P=0.042).【conclusion】pass an above research like draw a conclusion:Pass to examine the lung cancer cell CAⅨproteinase expression in the different environment level, CAⅨproteinase expression in the hypoxia environment is more obviously higher than the lung cancer cell in the normal environment, indicate that its expression relevant with hypoxia of lung cancer,The CAⅨexpression level may be benifit to diagnosis non-small cell lung cancer and estimate of the curative effect of Radiation therapy;The relativity of expression VEGF of analytical CAⅨ, Ki67 hints to hypoxia to help the tumor to organize of blood vessel born, but with cell enzyme amplification of the relation still need a further research.