纳米磁小体靶向药囊治疗人胆管癌细胞株移植瘤实验研究

目的:将纳米磁小体靶向药囊(TM5-FUNC)经尾静脉注射入胆管癌荷瘤裸鼠体内,通过埋植在移植瘤内的磁化支架所产生的磁靶向引导作用,TM5-FUNC选择性地聚集于裸鼠胆管癌移植瘤组织内;探讨此装置对人胆管癌的生长抑制作用。方法:建立人胆管癌裸鼠移植瘤模型,将裸鼠随机分成6组,通过尾静脉按分组方案给药,分别将TM5-FUNC 250mg/kg、200mg/kg和150mg/kg组列为高、中、低剂量组。计算各组裸鼠肿瘤体积、抑瘤率和肿瘤生长曲线。处死裸鼠后,将肿瘤标本置电镜下观察肿瘤组织超微结构改变情况。结果:结合内置支架的TM5-FUNC高、中剂量组的移植肿瘤体积在治疗后35d与对照组比较有显著差异(P<0.05);TM5-FUNC低剂量组的肿瘤体积与对照组比较则无明显差异(P>0.05)。其肿瘤的抑制率分别为:高剂量组39.6%、中剂量组14.6%、低剂量组7.9%。从高、中、低剂量TM5-FUNC干预组中可见,随着药物浓度的增高,肿瘤生长越缓,高剂量组肿瘤生长曲线变化最为缓慢,中剂量组次之,其余组曲线变化较为一致。电镜结果显示,TM5-FUNC对荷瘤裸鼠的肿瘤细胞有诱导凋亡作用,且随着药物浓度的增大,细胞凋亡的形态改变越为明显。结论:本课题组所研制的TM5-FUNC新剂型,在内磁场的导向作用下,能有效抑制人胆管癌裸鼠移植瘤的生长。

Inhibitory effects of TM5-FUNC on cholangiocarcinoma xenografts

Objective To investigate the therapeutic effects of TM5-FUNC on human cholangiocarcinoma xenografts in nude mice via tail vein injection. Methods Human cholangiocarcinoma xenografts was established in nude mice with the QBC939 cell line. The nude mice were randomly divided into 6 groups, including high dose TM5-FUNC treatment group (250 mg/kg), middle dose TM5-FUNC treatment group (200 mg/kg), low dose TM5-FUNC treatment group (150 mg/kg) and their control groups. TM5-FUNC was administrated via tail vein injection 20 days after tumor cells implantation. Tumor volume, inhibition ratio of tumor, and tumor growth curve were evaluated in each group. Micro-structure of xenografts in each group was also observed by electro-microscopy. Results Compared with those in the control groups, high dose and middle dose treatment groups demonstrated higher therapeutic effect (P<0.05). The inhibition ratio in high, middle and low dose treatment groups were 39.6%, 14.6% and 7.9%, respectively. The tumor growth curve of high, middle and low dose groups were declined accordingly. Apoptosis cells could be detected in high and middle dosage treatment groups. Conclusion The inhibitory effect of TM5-FUNC on human cholangiocarcinoma xenograft growth in the nude mice is clearly demonstrated.