浅蓝菌素对人成骨肉瘤细胞U2-OS在裸鼠体内生长抑制的作用

Cerulenin Inhibits Growth of Human Osteosarcoma(U2-OS) in Nude Mice

目的研究浅蓝菌素(cerulenin)对人成骨肉瘤细胞U2-OS在裸鼠体内生长抑制作用。方法建立人成骨肉瘤细胞U2-OS BALB/C裸鼠瘤模型。18只成瘤裸鼠按随机数字表分成3组,每组6只;对照组(DMSO溶剂)、低剂量cerulenin组(0.2 mL cerulenin配制液40 mg.kg-1.次-1)、高剂量cerulenin组(0.2 mL cerulenin配制液80 mg.kg-1.次-1)于腹腔隔日注射连续6次。动态观察3组肿瘤体积及裸鼠质量变化,用药结束后18 d处死裸鼠,测量瘤重、计算瘤重抑制率,测量肿瘤体积、计算肿瘤体积抑制率。肿瘤组织行形态学观察。TUNEL法检测肿瘤组织细胞凋亡情况。结果高、低剂量cerulenin组肿瘤体积抑制率分别为51.2%和24.2%,瘤重抑制率分别为49.1%和25.5%。各组间瘤体体积与瘤重比较,差异均有统计学意义(P<0.05)。瘤体组织学显示cerulenin组较对照组出现明显的细胞凋亡的超微结构改变,瘤细胞体积较小,多数细胞微绒毛消失,胞质密度增高。TUNEL法显示高、低剂量cerulenin组,对照组癌细胞凋亡率为(17.1±1.2)%、(10.3±0.8)%、(3.5±0.5)%,3组比较差异均有统计学意义(P<0.05)。结论 cerulenin能够有效诱导人成骨肉瘤细胞U2-OS在裸鼠体内凋亡,抑制肿瘤的生长。

Objective To investigate the inhibitory effect of fatty acid synthase inhibitor,cerulenin,on the growth of transplanted tumors of human osteosarcoma（U2-OS） in nude mice.Methods U2-OS human osteosarcoma xenografts were used as preclinical tumor models.The nude mice（18）bearing U2-OS human osteosarcoma were divided randomly into three groups with 6 mice in each group.0.2 mL DMSO solution、0.2 mL 40 mg·kg-1 cerulenin admixture solution and 0.2 mL 80 mg·kg-1 cerulenin admixture solution were intraperitoneal injected separately every other day for 6 times.After 18 days,we killed the mice.The weigh and size of the tumor were measured,while their inhibition ratio were evaluated.Histopathological changes of the tumors were observed.TUNEL apoptosis assay kit to examine U2-OS cell＇s apoptosis.Results Weight inhibited ratio was 49.1% in low dose cerulenin treatment group,while 25.5% in the high.Volume inhibited ratio was 51.2% and 24.2% differently in two treatment groups.The data were all significantly different in the three groups（P0.05）.The histopathological features showed that death of U2-OS cells treated by cerulenin was associated with apoptosis characterized by disappeared cell microvillus and high density cytoplasm.High dose cerulenin induced（17.1±1.2）% apoptosis,while the low induced（10.3±0.8）%,both were much higher than the data（3.5±0.5）% in control group.Apoptotic index were significantly different in the three groups（P0.05）.Conclusion Cerulenin could effectively inhibit the growth of human osteosarcoma（U2-OS）cells in vivo.The mechanism of cell death may be correlated with apoptosis.