摘要
目的:构建小鼠恶性黑素瘤模型,在体研究脂氧素A4(LXA4)类似物BML-111对恶性黑素瘤生长的影响,并初步探讨其可能的作用机制。方法:将人源恶性黑素瘤A375细胞接种于裸鼠腋下,构建小鼠恶性黑素瘤模型,造模成功后将实验动物随机分为磷酸盐缓冲溶液(PBS)组和BML-111组进行干预治疗,观察并记录小鼠的生活状态和肿瘤生长情况。给药结束后,测量小鼠肿瘤体积,制作肿瘤生长曲线;剥取肿瘤组织称重,计算肿瘤生长抑制率(IR);肿瘤组织经苏木精-伊红(HE)染色后,采用免疫组化检测血管内皮细胞生长因子(VEGF)表达水平;收集小鼠血清,采用酶联免疫吸附试验(ELISA)检测血清中VEGF表达。结果:与PBS组相比,BML-111组小鼠肿瘤生长曲线较平缓,肿瘤体积明显小于PBS组小鼠(P<0.05);BML-111组小鼠IR(57.12%)明显大于PBS组(0.01%)(P<0.05)。BML-111组肿瘤组织病理检查示多处坏死灶,肿瘤细胞出现细胞溶解、破碎,核固缩及细胞间隙增大。免疫组化和ELISA均显示BML-111组肿瘤组织和血清中VEGF表达较PBS组明显减少(P<0.05)。结论:BML-111可显著抑制小鼠恶性黑素瘤生长,其机制可能是BML-111通过抑制与肿瘤生长相关的血管生成,从而发挥抑瘤效应。
Objective: A mouse malignant melanoma model is developed to study the effect of lipoxin A4 analogue BML-111 on malignant melanoma in vivo and its possible mechanism. Methods: Human malignant melanoma A375 cells were inoculated subaxillary in nude mice to construct a mouse malignant melanoma model. After the mouse model was established, the experimental animals were randomly divided into PBS control group and BML-111 group for further treatment. The living conditions and tumor growth of the mice were observed and recorded. After treatment, tumor growth curve and tumor growth inhibition rate(IR) were measured.The tumor tissue was examined histologically with Haemotoxylin and Eosin(H&E) staining. The vascular endothelial growth factor(VEGF) expression was detected by immunohistochemical method and immunoenzyme-linked assay(ELISA). Results: Compared with PBS control group, the growth curve of BML-111 group was flat, the tumor volume was significantly smaller than that of control group(P<0.05), and the tumor inhibition rate of BML-111 group(57.12%) was significantly higher than that of control group(0.01%)(P<0.05). Histopathological examination showed that the tumor cells in BML-111 group had multiple foci of necrosis, and most of the tumor cells were dissolved and fragmented with nucleosome pyknosis and enlarged intercellular spaces. Immunohistochemistry and ELISA revealed that the level of VEGF expression from both tumor tissue and serum of BML-111 group was significantly lower than those of control group(P<0.05). Conclusion: BML-111 can significantly inhibit the growth of malignant melanoma in mice model. The mechanism by which BML-111 exerts anti-tumor effects might be through inhibiting angiogenesis related to tumor growth.
作者
李娟
曾蓁
沈柱
李灵
LI Juan;ZENG Zhen;SHEN Zhu
出处
《临床皮肤科杂志》
CAS
CSCD
北大核心
2020年第10期589-593,共5页
Journal of Clinical Dermatology
基金
四川省卫生厅课题(30504010129)资助项目。
