C57BL6小鼠前列腺癌原位移植瘤模型的建立及其MRI表现

Establishment of An Orthotopic Transplantation Tumor Model of Prostate Cancer in C57BL6 Mice and Its MRI Manifestations

目的采用瘤组织块原位移植法建立C57BL6小鼠前列腺癌原位移植瘤模型,观察其MRI表现,为研究前列腺癌的生长转移机制及其药物实验提供适宜的动物模型。材料与方法采用随机数字表法在35只6~8周龄C57BL6雄鼠中选出4只,将RM-1前列腺癌肿瘤细胞注射到小鼠背部皮下,每只注射0.1ml。待瘤组织块生长至1cm3时剥离出肿瘤组织,并裁剪为合适大小后,借助注射器种植到30只同周龄小鼠的前列腺内,建立小鼠前列腺癌原位移植瘤模型。第8天,从30只荷瘤鼠中采用随机数字表法选出6只,采用3.0TMR进行扫描。扫描结束后处死小鼠并取出瘤组织,将游标卡尺与MRI测量结果进行对比,最后进行病理学检查。结果建模1周后,29只实验小鼠可触及下腹部肿块;前列腺癌原位移植瘤T2WI呈中等信号,肿瘤向前膨出,将包膜挤出一定角度和高度提示包膜受累;病理切片可见大量瘤细胞呈条索状或散在成团杂乱分布于前列腺体间质中,肿瘤细胞形态不规则,呈多形性,核质比增大,可见异常病理性核分裂象。此模型成功率为96.7%(29/30),周围淋巴结转移率为96.7%(29/30),腹水形成率为96.7%(29/30),肝转移发生率为93.3%(28/30),肾转移发生率为0.33%(1/30),肉眼未见明显肺部转移,小鼠平均生存时间(12.7±1.8)d。MRI与游标卡尺测量肿瘤最大直径差异无统计学意义(P>0.05)。结论此种方法建立的前列腺癌原位模型操作简单、建模周期短、移植瘤成功率高,且其影像学表现与人类前列腺癌相似,可作为观察人类前列腺癌的动物模型。

Purpose An orthotopic transplantation tumor model of prostate cancer in C57BL6 mice was established with the tumor tissue mass orthotopic transplantation method to observe its MRI manifestations,and to provide an appropriate animal model for explomouseion of the mechanism of the growth and metastasis of prostate cancer and its drug experiment.Materials and Methods Four mice were randomly selected from 35 C57BL6 male mice of 6-8 weeks,RM-1 prostate cancer cells were subcutaneously injected to the back of each mouse,with 0.1 ml in each mouse.Tumor tissue was stripped when the tumor tissue mass grew to 1 cm3,after being cut into appropriate size,it was implanted in the prostate of 30 mice of the same yearling by means of a syringe,and an orthotopic transplantation tumor model of mouse prostate cancer was established.On day 8,6 mice were randomly selected from 30 mice with tumor using the random number table method,and scanned with 3.0T MR.After scanning,they were executed and the tumor tissue was removed.Vernier calipers were used to compare with MRI measurements,and finally pathological examination was conducted.Results One week after modeling,there were palpable abdominal masses in 29 mice;the T2WI image of the orthotopic transplantation tumor of prostate cancer showed a moderate signal tumor.The tumor bulged forward,and the envelope was squeezed to a certain angle and height,suggesting the involvement of the envelope.The pathological sections showed that a large number of tumor cells were streak or scattered in the mesenchyme of the body of prostate.The tumor cells were irregular and polymorphous,with enlarged nucleo-cytoplasmic ratio.The abnormal histopathological mitotic figure was seen.The success rate of this model was as high as 96.7%(29/30),peripheral lymph node metastasis rate was 96.7%(29/30),ascites formation rate was 96.7%(29/30),incidence of liver metastasis was 93.3%(28/30),and renal transfer rate was 0.33%(1/30).No apparent lung metastases were visible to the naked eye,and the average survival time of the mice was (12.7±1.8) d.There was no significant difference between the maximum diameters of tumor measured by MRI and vernier calipers (P>0.05).Conclusion The orthotopic transplantation tumor model of prostate cancer is featured by simple operation,short modeling cycle,high success rate of transplantation tumor,with image manifestations similar to human prostate cancer,and thus can be used as an animal model for observation of human prostate cancer.