人肺癌组织免疫缺陷鼠移植瘤模型的建立

Establishment of patient-derived xenotransplantation models for non-small cell lung cancer in immune deficient mice

背景与目的:目前提倡对肿瘤实行靶向药物个性化治疗,建立不同通路异常肿瘤的动物模型成为必需。本研究探讨人非小细胞肺癌手术标本免疫缺陷鼠皮下移植瘤模型的建立及建模的适宜条件和方法。方法:选取BALB/c裸小鼠、SCID小鼠及NOD/scid小鼠各16只,采用套管针四点左边两块、右边一块式接种法,16例患者中每例患者的肿瘤组织标本分别接种于每个鼠种的一只。观察不同种免疫缺陷鼠移植瘤成瘤率、成瘤潜伏时间、肿瘤体积倍增时间、自然病亡率及左右两边接种点的成瘤率和头尾部成瘤点处死时大于1cm的比率,并鉴别移植瘤形态结构与来源组织的一致性及鉴定移植瘤是否为上皮来源。结果:总成瘤率为75%,其中4个病例只有SCID小鼠成瘤,2个病例只有BALB/c裸小鼠成瘤,NOD/scid小鼠无一例单独成瘤。不同种免疫缺陷鼠移植瘤成瘤率、成瘤潜伏时间和肿瘤体积倍增时间及左右两边接种点的成瘤率差异无统计学意义。SCID小鼠成瘤率最高,为56.25%;NOD/scid小鼠自然病亡率为25%,BALB/c裸小鼠、SCID小鼠在观察期内无一例病亡;处死时头部成瘤点大于1cm的比率(56.52%)与尾部成瘤点大于1cm的比率(25%)相比差异有统计学意义(P=0.037);所有移植瘤苏木精-伊红染色显示其形态结构均与来源组织一致,所有移植瘤角蛋白免疫组化均为阳性,显示移植瘤均为上皮来源。结论:四点两块套管针接种BALB/c裸小鼠和SCID小鼠各一只的方法能很好地建立非小细胞肺癌手术标本免疫缺陷鼠皮下移植瘤模型,头部移植瘤的生长速度明显快于尾部。

Background and Objective： Targeted therapies have become a valuable therapeutic option for cancer. Establishment of different animal tumor models has become necessary. This study was to establish xenotransplantation models for patient-derived non-small cell lung cancer （NSCLC） in immune deficient mice. Methods. Immune deficient mice, BALB/ C-nu, NOD/scid and SCID, 16 in each strain, were used. Sixteen tumor specimens were obtained from patients with NSCLC. Each specimen was subcutaneously transplanted into one mouse from each of the three strains. The tumor formation rate, time to tumor engraftment, tumor volume doubling time were recorded and compared among the three strains of mice. Histology of xenograft tumors was examined. Results.The total tumor formation rate was 75% （12/16）. The tumor formation rate was the highest in SCID mice （56.25%）. Only four tumors were engrafted in SCID mice, and two in BALB/ C-nu mice. The tumor formation rate, time to tumor engraftment, and tumor volume doubling time were not significantly different among the three strains of mice. The incidence of tumor size over lcm in the upper flanks of the mice （56.25%） was significantly higher than that in the lower flanks （25%） （P= 0.037）. Haematoxylin Eosin staining revealed a high degree of histological similarity between all xenograft and the parental tumors. Conclusions. We have established xenotransplantation models for patient-derived NSCLC with a success rate of 75% in BALB/C-nu and SCID mice. The xenograft tumors have the same histological features to those of their parental tumors.