超声介导的载药微泡对裸鼠卵巢癌皮下移植瘤的抑制作用

Inhibitory effect of ultrasonic-mediated drug-loaded microvesicles on subcutaneous xenograft of ovarian cancer in nude mice

目的探讨超声介导的载药微泡对裸鼠卵巢癌皮下移植瘤的抑制作用。方法以人卵巢癌A2780细胞建立裸鼠皮下转移瘤模型。将建模的40只小鼠随机平均分为4组并给予不同处理方式,A组:向裸鼠尾静脉中注入顺铂溶液和超声微泡后予超声辐照;B组:向裸鼠尾静脉中注入顺铂溶液和超声微泡,不予超声辐照;C组:向裸鼠尾静脉中注入生理盐水后予以超声辐照;D组:不做任何处理。4组裸鼠均每3天处理1次,共处理6次。处理完成后比较4组小鼠肿瘤体积、肿瘤部位感兴趣区峰值强度(peak intensity,PI)以及病理切片结果。多组间比较采用方差分析,进一步两两比较采用SNK法,组内治疗前后的比较采用t检验。结果(1)与治疗前比较,仅A组治疗后肿瘤体积显著缩小(t=-7.642,P<0.01),B、C、D组治疗后肿瘤体积显著增大(t=-7.841、-21.052、-10.051,均P<0.01);4组小鼠治疗后肿瘤体积的差异有统计学意义(F=13.219,P<0.01),其中A组肿瘤体积显著小于其他各组(P<0.01)。(2)与治疗前比较,仅A组治疗后肿瘤部位感兴趣区PI显著缩小(t=-11.746,P<0.01),B、C、D组治疗后肿瘤部位感兴趣区PI均无明显变化(t=1.173、-1.351、-2.014,均P>0.05);4组小鼠治疗后肿瘤部位感兴趣区PI的差异有统计学意义(F=61.101,P<0.01),其中A组肿瘤部位感兴趣区PI显著小于其他各组(P<0.01)。(3)病理结果提示A、B组小鼠肿瘤细胞坏死程度均较明显,其中A组较B组更为明显。结论超声介导的载药微泡可在提高肿瘤部位药物浓度的同时,避免药物受到外部环境破坏,从而保持药物原有的代谢性质,实现药物靶向释放及精准治疗的目的,有可能为老年卵巢癌患者提供一种新的肿瘤辅助化疗方案。

Objective To investigate the therapeutic effect of ultrasound-mediated drug loaded microbubbles on ovarian cancer xenografts in nude mice.Methods Human ovarian cancer A2780 cells were used to establish subcutaneous metastasis model in nude mice.40 mice were randomly divided into 4 groups and given different intervention methods.Group A:DDP solution and ultrasound microbubbles were injected into the tail artery of nude mice and then irradiated by ultrasound;Group B:DDP solution and ultrasound microbubbles were injected into the tail artery of nude mice without ultrasound irradiation;Group C:Normal saline was injected into the tail artery of nude mice and then was irradiated by ultrasound;Group D:No treatment was done.Nude mice in the four groups were treated once every 3 days for 6 times.After treatment,tumor volume,peak intensity(PI)of tumor site and pathological section were compared among the four groups.The analysis of variance was used for the comparison between the groups,SNK method was used for the further pair comparison,and t test was used for the comparison before and after treatment within the group.Results Compared with before treatment,the tumor volume of group A was significantly reduced after treatment(t=-7.642,P<0.01),and that of groups B,C and D was significantly increased after treatment(t=-7.841,-21.052,-10.051,P<0.01).After treatment,there was statistically significant difference in tumor volume among the four groups(F=13.219,P<0.01),and the tumor volume of group A was significantly smaller than that of the other groups(P<0.01).Compared with before treatment,PI of ROI of tumor site decreased significantly in group A(t=-11.746,P<0.01),while there was no significant change in PI of ROI of tumor site in groups B,C and D(t=1.173,-1.351,-2.014,P>0.05).After treatment,there was statistically significant difference in PI of ROI of tumor site among the 4 groups(F=61.101,P<0.01),and the PI of ROI of tumor site in group A was significantly lower than that in the other groups(P<0.01).The pathological results showed that the necrosis degree of tumor cells in group A and B was obvious,and the necrosis degree of tumor cell in group A was more obvious than that in group B.Conclusion Ultrasound mediated drug loaded microbubbles can improve the drug concentration at tumor site,avoid the destruction of external environment,maintain the original metabolic properties of drugs,and achieve the goal of drug targeted release and precise treatment.It is possible to provide a new adjuvant chemotherapy for elderly patients with ovarian cancer.