膀胱灌注米替福新治疗原位非肌层浸润性膀胱癌的研究

Intravesical instillation of Miltefosine in the treatment of non muscle invasive bladder cancer in situ

目的研究经尿道膀胱灌注米替福新对裸鼠原位非肌层浸润性膀胱癌的治疗作用。方法30只裸鼠采用膀胱壁内注射人膀胱移行细胞癌细胞(T24细胞)的方法制备裸鼠原位非肌层浸润性膀胱癌模型,造模后第3天分为模型组、盐酸吉西他滨组(150mg/kg)和米替福新高、中、低剂量组(分别为6mg/kg、4mg/kg和2mg/kg),每组6只,每周经尿道膀胱灌注给药1次,给药体积30μL/只;另选取6只裸鼠膀胱壁内注射等体积的生理盐水(正常组),实验结束时处死动物,测定肿瘤质量、大体及镜下观察小鼠的膀胱病理改变情况。结果与正常组比较,模型组膀胱显著扩张,镜检可见肿瘤几乎占满整个膀胱腔,并有部分突破膀胱外膜向外生长。与模型组比较,吉西他滨组膀胱扩张不明显,肿瘤质量显著减小,抑瘤率达91.9%,镜检膀胱黏膜及黏膜下层可见少量肿瘤细胞,未见浸润至肌层;米替福新高剂量组膀胱轻度扩张,肿瘤显著减轻,抑瘤率72.4%;米替福新中、低剂量组的肿瘤细胞均已浸润至膀胱肌层,少部分突破膀胱外膜向外生长,肿瘤质量略有降低,抑瘤率分别为29.8%、18.9%。结论在本研究中高剂量(6mg/kg)的米替福新膀胱灌注对原位非肌层浸润性膀胱癌具有一定的治疗作用。

Objective To study the therapeutic effect of transurethral intravesical instillation of miltefosine on nude mice with non muscle invasive bladder cancer.Methods 30 nude mice were injected with human bladder transitional cell carcinoma cell(T24 cells)in the bladder wall to prepare nude mice model of non muscle invasive bladder cancer.After three days,they were divided into five groups:model group,gemcitabine group(150mg/kg),and miltefosine groups(the doese of miltefosine were 6mg/kg,4mg/kg and 2mg/kg,respectively),with 6 rats in each group.The mice were administered by transurethral bladder perfusion once a week with a volume of 30μL/mouse.The normal group and the model group was perfused with the same amount of normal saline.At the end of the experiment,the mice were sacrificed,the tumor mass was measured,and the pathological changes of the bladder of the mice were observed by macroscopy and histopathological examexamination.Results Compared with the normal group,the bladder in the model group was significantly dilated.It showed that the tumor almost filled the whole bladder cavity,and some of them broke through the outer membrane of the bladder and grew outwardby by histopathological examination.Compared with the model group,the bladder of gemcitabine hydrochloride group was haddly expanded the tumor mass was decreased significantly,and the tumor inhibition rate was 91.9%.A small number of tumor cells could be seen in bladder mucosa and submucosa under microscope,and no infiltration into muscle layer was found;In the high dose group,the bladder was slightly dilated,the tumor was reduced significantly,and the tumor inhibition rate was 72.4%;The tumor cells in the middle and low dose groups of miltefosine had infiltrated into the bladder muscle layer,a small part of them broke through the bladder outer membrane and grew outward,the tumor mass decreased slightly,and the tumor inhibition rates were 29.8%and 18.9%respectively.Conclusion In this experiments,high dose(6mg/kg)perfusion of the miltefosine in bladder has a certain therapeutic effect on non-muscle invasive bladder cancer in situ.