榄香烯脂质体结合超声空化技术对裸鼠异位瘤的抑制作用及毒性评价

Evaluation of the inhibitory action and toxicity of elemene liposome combining ultrasound cavitation on the ectopic tumor of the nude mice model

目的:以榄香烯脂质体(EL)作为对照药物,评价EL结合超声空化技术在抗肿瘤疗效及降低不良反应中的作用。方法:建立大鼠胶质瘤C6细胞裸鼠皮下肿瘤模型并通过尾静脉注射方式给药,EL(浓度为5mg/m L)给药剂量为50mg/kg(0.1m L/10g)。实验分5组(n=7):0.9%氯化钠溶液(空白对照)组、榄香烯脂质体(EL)组、榄香烯脂质体+超声造影剂(EL+MB)组、榄香烯脂质体+超声(EL+US)组、榄香烯脂质体+超声造影剂+超声(EL+MB+US)组,每隔2d给药1次,共给药3次,检测裸鼠肿瘤体积变化、肿瘤质量变化、体质量变化和血液白细胞数等指标,取肿瘤组织,HE染色观察肿瘤组织形态学变化,TUNEL试剂盒检测肿瘤细胞凋亡程度,观察超声造影剂联合超声对EL抗肿瘤的疗效与血液学毒性的影响。结果:与EL组比,EL+MB+US组对肿瘤体积增长的抑制作用强(P<0.05),裸鼠体质量变化小,肿瘤细胞凋亡程度增加,白细胞数降低量减小(P<0.05)。结论:与EL相比,EL+MB+US可以更有效地发挥对肿瘤生长的抑制作用,提高裸鼠生存质量,降低血液学毒性,可以作为一个新的肿瘤药物递送系统进一步开发研究。

Objective： To evaluate the inhibitory action and toxicity of elemene liposome （EL） combining ultrasonic cavitation on the entopic tumor for the nude mice model. Methods： The inhibitory efficacy was studied using C6 cells bearing armpit tumor model. Mice were assigned to 5 groups （n=7） as follows： group 1 for saline, group 2 for EL, group 3 for EL＋MB, group 4 for EL＋US and group 5 for EL＋MB＋US. Mice were administered via tail vein at the dosage of 50 mg/kg amount to 0.1 mL/10 g （injection solution/mice weight）, 1 time per 2 d, 3 times in all. Tumor volume, tumor weight change, body weight growth rate were all measued. The white blood cell count （WBC） at the end point was also tested. Results： Compared with EL, EL＋MB＋US showed higher tumor growth inhibition, fewer mice body weight change and white blood count change （P〈0.05） in the armpit tumor model. Conclusion： With better anti-tumor activity and lower blood toxicity, EL＋MB＋US may be developed as a new cancer targeted delivery system.