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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。
Objective: In recent years, the etiology of metabolism and tumor pathogenesis has become a hot spot, while the incidence of lung cancer is still the highest incidence of malignant tumors and mortality in this study to build a stable and easy to operate in situ orthotopic lung cancer model and preliminary study of metabolism Expression of related pathways in this orthotopic xenograft model. Methods: Ten male BABL / c nude mice (6-8 weeks old) were selected to optimize anesthesia and surgical procedures. A549 lung cancer cells with 5 × 106 cells were transplanted into the tumor. The tumor formation rate, formation site, Morphology, proliferation and differentiation. Another four nude mice under the same conditions for surgery blank control. At the same time, the expression of STAT3, AKT and m TOR were detected. Results: The optimal anesthesia condition was 75 mg / kg sodium pentobarbital intraperitoneal injection. The lung formation rate was 80.0% after tracheal transplantation in the improved operation. The tumors formed mostly with the upper right lobe and obvious adenocarcinoma , The degree of differentiation was lower. The expression of proliferating cell nuclear antigen (PCNA) in the xenografts was higher than that in the lung tissues and was highly expressed. Signal transduction and activator of transcription 3 (STAT3), protein kinase B (PKB), mammalian mammalian target protein (mammalian) pTT / AKT, pm TOR / m TOR were significantly higher than those in normal lung tissues (t = -4.381, -4.462, - 4.951; P = 0.041, 0.011, 0.038). CONCLUSION: Transplantation of transbronchial transurethral resection can establish a simple, low-cost and highly efficient A549 cell lung cancer xenograft model. Metabolic-related pathways also play a role in the development of lung cancer.