代谢相关通路在人肺癌细胞系A549原位移植瘤模型中的表达

发布时间：2018-02-25 22:38

  本文关键词： 肺癌 A 原位移植 信号传导与转录激活因子 蛋白激酶B 哺乳动物雷帕霉素靶蛋白　出处：《重庆医科大学学报》2017年07期 　论文类型：期刊论文

【摘要】：目的:近年来,代谢与肿瘤发病的病因学研究已经成为热点,同时肺癌仍居恶性肿瘤发病率和死亡率榜首,本研究拟构建一个稳定易操作的肺癌原位移植瘤模型,并初步探讨代谢相关通路在该原位移植瘤模型中的表达。方法:选取雄性6~8周龄BABL/c裸鼠10只,优化麻醉用药及手术操作步骤,经气管移植5×106个细胞的A549肺癌细胞成瘤,观察移植瘤形成率、形成部位、大体形态、增殖分化程度。另取4只相同条件裸鼠进行手术空白对照。同时检测代谢相关通路蛋白STAT3、AKT和m TOR的表达情况等。结果:手术最佳麻醉条件为75 mg/kg戊巴比妥钠腹腔注射;改进操作后经气管移植的小鼠肺癌形成率为80.0%;肿瘤形成以右肺上叶居多,呈明显腺癌结构,分化程度较低,移植瘤组织增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达高于肺组织,呈高表达状态。肿瘤负荷肺组织代谢相关通路蛋白信号传导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)、蛋白激酶B(protein kinase B,PKB即AKT)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)的磷酸化水平即p STAT3/STAT3、p AKT/AKT、p-m TOR/m TOR比值均高于正常肺组织,差异具有统计学意义(t=-4.381,-4.462,-4.951;P=0.041,0.011,0.038)。结论:通过改良经气管移植手术方式,可以构建一种操作简单、低成本、高效稳定的A549细胞肺癌移植瘤模型;代谢相关通路在肺癌的发生发展中也发挥了一定作用。
[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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