转基因小鼠源性胰腺癌原位移植瘤模型的构建与评价

Establishment and evaluation of an orthotopic transplantation tumor model derived from transgenic mouse with spontaneous pancreatic cancer

目的构建转基因LSL-KrasG12D/+LSL-Trp53R172H/+Pdx1-Cre(KPC)小鼠胰腺癌原位移植瘤模型,为研究胰腺癌的发展机制和治疗策略提供稳定、可靠的药物临床前研究动物模型。方法将KPC转基因小鼠的自发胰腺癌的组织块进行C57BL/6J小鼠胰腺原位移植,利用超声进行肿瘤监测,对原发肿瘤和传代肿瘤进行苏木精-伊红(HE)染色和免疫荧光染色评价模型的肿瘤病理学特征。结果KPC小鼠的自发肿瘤能够在C57BL/6J小鼠的胰腺上稳定生长,肿瘤增殖指标Ki67、基质纤维化标志物α-SMA、免疫细胞标志物CD45和CD206均稳定表达,该模型能够稳定地保留原发胰腺癌病理学特征,并发生与临床胰腺癌患者相似的广泛转移。结论成功建立转基因小鼠源性胰腺癌原位移植瘤模型,该模型能够模拟出胰腺癌的基质环境和免疫细胞浸润情况,具有较好的稳定性和均一性,可以作为研究胰腺癌进展和治疗策略的有效药物临床前研究模型。

Objective To establish an orthotopic transplantation tumor model of pancreatic cancer derived from transgenic LSL-KrasG12D/+LSL-Trp53R172H/+Pdx1-Cre(KPC)mice.To provide a stable and reliable drug preclinical research animal model to study the developmental mechanism and treatment strategies of pancreatic cancer.Methods Tumor tissue derived from KPC transgenic mice with spontaneous pancreatic cancer was transplanted into the C57BL/6J mouse pancreas.Ultrasound was used to monitor tumor growth.HE and immunofluorescence staining was used to evaluate the pathological characteristics of this model.Results The tumor derived from KPC mice grew steadily on the pancreas of C57BL/6J mice.Tumor cell proliferation index Ki67,matrix fibrosis markerαSMA,and immune cell markers CD45 and CD206 were all stably expressed in the tumor.The model stably retained the pathological features of primary pancreatic cancer.Widespread tumor metastases,which were similar to those observed in patients with pancreatic cancer,developed in this model.Conclusions An orthotopic transplantation model derived from a transgenic mouse with spontaneous pancreatic cancer was established successfully.The model simulates the stromal environment and immune cell infiltration of pancreatic cancer and retains strong stability and uniformity with the original tumor.It can be used as an effective drug preclinical research model to study pancreatic cancer progression and treatment strategies.