简易肾癌及膀胱癌原位肿瘤模型的建立与应用研究

Establishment and application of simple orthotopic kidney and bladder tumor models

目的建立一种操作简单、稳定可靠的肾癌及膀胱癌原位癌模型,并运用于抗癌药效评价工作。方法将人肾癌肿瘤组织块穿刺接种到肾实质组织中,建立肾癌原位肿瘤模型;用留置针机械摩擦损伤膀胱黏膜,人膀胱癌细胞悬液暴露法建立膀胱癌原位肿瘤模型。通过小动物B超和荷瘤组织的HE染色确定模型建立的可靠性,并采用该模型对硝羟喹啉(nitroxoline,NTX)的体内抗肿瘤药效进行初步药效评价。结果术后2周通过B超可见肿瘤发生;组织病理HE染色显示肾癌原位模型肿瘤呈现浸润性生长,膀胱癌模型可见明显突向膀胱腔的癌组织团块。NTX体内药效评价中,60 mg/kg NTX对肾癌原位肿瘤抑制率为57.5%,30 mg/kg NTX对膀胱癌原位肿瘤抑制率为48.8%。结论利用上述方法建立的肾癌及膀胱癌原位肿瘤模型简单、实用,是评价治疗肾癌和膀胱癌抗癌药物的可靠方法。

Objective To establish a simple and useful kidney or bladder orthotopic tumor model used in preclinical pharmacodynamic evaluation. Methods Mouse model of orthotopic renal cancer were established by subrenal capsule implantation. After aspirating urine and irrigating bladder with PBS,the bladder urothelium was slightly impaired to establish the orthotopic bladder tumor model. Then,B-Ultrasound and HE staining were used to confirm the availability. Results Tumors could be seen 2 weeks after surgery,accompanied by body mass loss of the mice. HE staining showed that the tumor cells acted as infiltrative growth. The growth of tumor was inhibited by NTX in vivo,the tumor mass inhibitory rate of the KCC-853 orthotopic tumor model was 57. 5% of 60 mg / kg NTX treatment and 48. 8% in the T24 orthotopic tumor model of 30 mg / kg NTX treatment. Conclusion Our methods for establishing the orthotopic kidney or bladder tumor model are simple and practical. The results indicate that nitroxoline has potential antitumor activity.