聚焦超声对人宫颈癌裸鼠皮下移植瘤生物学特性的影响

Effects of focused ultrasound on biological characteristics of cervical tumor transplanted subcutaneously in nude mice

目的:观察聚焦超声对人宫颈癌裸鼠皮下移植瘤治疗作用及对治疗靶区边缘肿瘤组织生物学特性的影响。方法:32例人宫颈癌裸鼠皮下移植瘤模型,不同剂量聚焦超声辐照后,不同时间观察荷瘤鼠的一般生命体征、瘤体生长情况。取辐照靶区及靶区边缘肿瘤组织,观察组织病理学及超微结构变化。原位末端标记法检测瘤细胞凋亡,免疫组化检测Bax、Bcl-2、PCNA及MMP-9的表达。结果:聚焦超声可明显抑制人宫颈癌裸鼠皮下移植瘤的生长,随辐照剂量增加其抑制作用亦增强。病理组织学观察可见各治疗组靶区变性、坏死,核结构破坏。靶区边缘肿瘤细胞肿胀、排列疏松,电镜示线粒体肿胀,胞质空化泡形成,核结构变化不显著。TUNEL检测靶区边缘瘤组织凋亡细胞数目增多,免疫组化检测Bax表达上调,Bcl-2表达下调,PCNA及MMP-9蛋白表达减弱。结论:聚焦超声可明显破坏人宫颈癌裸鼠皮下移植瘤细胞并抑制肿瘤生长,对辐照靶区边缘肿瘤细胞有促进凋亡作用,该过程可能与聚焦超声热效应激活线粒体介导的细胞凋亡信号通路有关。

Objective：To observe the treating effect of focused ultrasound on human cervical tumor transplanted subcutaneously in nude mice.Methods：After irradiated with different dose of focused ultrasound,the thirty-two nude mice which transplanted subcutaneously with human cervical cancer were observed for the growth of the subcutaneously transplanted tumor and general vital sign and its effects on the biological characteristics of tumor tissues on the rim of the targeted areas at the different time.Target areas and the rim of the targeted areas in tumor samples were examined by light microscope and electron microscope for the change of histopathology and ultra-structure.Apoptosis was detected by TUNEL.The immunohistochemical method was applied to investigate the expressions of Bax,Bcl-2,PCNA and MMP-9.Results：Focused ultrasound had evident inhibitory effect on the growth of transplanted subcutaneously human cervical tumor in nude mice and the effect was positively related to the dose.Denaturation,necrosis and the damage of nuclear structure were found in targeted areas of each treatment group through pathohistological observation.Tumor cell that on the rim of the targeted areas were swelling and loosing arranged.Ultrastructural investigations showed mitochondrion swelling and the formation of cytoplasm cavitations bubbles,but the change of nuclear structure was not significant.Compared with that of unirradiated areas,apoptosis rate of tumor cell in the rim of the targeted areas was increasing,the expression of Bax was up-regulated and Bcl-2 was down regulated,and the expressions of PCNA and MMP-9 protein weakened.Conclusions：Focused ultrasound could significantly damage the tumor cells of human cervical cancer transplanted subcutaneously in nude mice tumor and induced apoptosis of tumor cell on the rim of the targeted areas significantly.The process maybe related to the mitochondria-mediated cell apoptosis signal passage that activated by the thermal effect of focused ultrasound.