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代謝相關通路在人肺癌細胞系A549原位移植瘤模型中的表達

發(fā)布時間:2018-02-25 22:38

  本文關鍵詞: 肺癌 A 原位移植 信號傳導與轉錄激活因子 蛋白激酶B 哺乳動物雷帕霉素靶蛋白 出處:《重慶醫(yī)科大學學報》2017年07期  論文類型:期刊論文


【摘要】:目的:近年來,代謝與腫瘤發(fā)病的病因學研究已經成為熱點,同時肺癌仍居惡性腫瘤發(fā)病率和死亡率榜首,本研究擬構建一個穩(wěn)定易操作的肺癌原位移植瘤模型,并初步探討代謝相關通路在該原位移植瘤模型中的表達。方法:選取雄性6~8周齡BABL/c裸鼠10只,優(yōu)化麻醉用藥及手術操作步驟,經氣管移植5×106個細胞的A549肺癌細胞成瘤,觀察移植瘤形成率、形成部位、大體形態(tài)、增殖分化程度。另取4只相同條件裸鼠進行手術空白對照。同時檢測代謝相關通路蛋白STAT3、AKT和m TOR的表達情況等。結果:手術最佳麻醉條件為75 mg/kg戊巴比妥鈉腹腔注射;改進操作后經氣管移植的小鼠肺癌形成率為80.0%;腫瘤形成以右肺上葉居多,呈明顯腺癌結構,分化程度較低,移植瘤組織增殖細胞核抗原(proliferating cell nuclear antigen,PCNA)的表達高于肺組織,呈高表達狀態(tài)。腫瘤負荷肺組織代謝相關通路蛋白信號傳導與轉錄激活因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B(protein kinase B,PKB即AKT)、哺乳動物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)的磷酸化水平即p STAT3/STAT3、p AKT/AKT、p-m TOR/m TOR比值均高于正常肺組織,差異具有統(tǒng)計學意義(t=-4.381,-4.462,-4.951;P=0.041,0.011,0.038)。結論:通過改良經氣管移植手術方式,可以構建一種操作簡單、低成本、高效穩(wěn)定的A549細胞肺癌移植瘤模型;代謝相關通路在肺癌的發(fā)生發(fā)展中也發(fā)揮了一定作用。
[Abstract]:Objective: in recent years, the etiology of metabolism and tumor has become a hot topic, and lung cancer still ranks the first in the incidence and mortality of malignant tumors. In this study, a stable and easy to operate lung cancer orthotopic transplanted tumor model was established. Methods: 10 male BABL/c nude mice aged 6 weeks and 8 weeks old were selected to optimize anesthetic and operative procedures, and 5 脳 106 cells of lung cancer were transplanted through trachea. To observe the formation rate, site and shape of transplanted tumor. The degree of proliferation and differentiation. Four nude mice with the same condition were taken for operation blank control. Meanwhile, the expression of STAT3AK T and m TOR were detected. Results: the optimal anesthesia condition was 75 mg/kg pentobarbital sodium intraperitoneal injection. The formation rate of lung cancer in mice transplanted by trachea was 80.0.The tumor formation was mainly in the upper lobe of the right lung, with a distinct adenocarcinoma structure and low differentiation. The expression of proliferating cell nuclear antigenPCNA (PCNA) in transplanted tumor tissue was higher than that in lung tissue, and the expression of proliferating cell nuclear antigenPCNA in transplanted tumor tissue was higher than that in lung tissue. The protein signal transduction and transcriptional activator 3signal transducer and activator of transcription 3 statin 3, protein kinase B protein kinase kinase PKB, mammalian rapamycin target protein mammalian target of rapamycin receptor phosphorylated water. The p-m TOR/m TOR ratio of p-STAT3 / STAT3T / AKT / AKT was higher than that of normal lung tissue. The difference was statistically significant (P < 0.05). Conclusion: a simple, low cost, high efficient and stable model of lung cancer transplantation of A549 cell can be constructed by modified transtracheal transplantation. Metabolic pathways also play a role in the development of lung cancer.
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