蜂毒素(Mel)对裸鼠骨肉瘤的抑制作用与影响肿瘤血管生成、细胞增殖和凋亡的关系

 目的 探讨蜂毒素(melittin,Mel)抑制骨肉瘤裸鼠移植瘤的作用机制。方法 用SD大鼠成骨肉瘤UMR-106细胞株建立骨肉瘤原位移植瘤裸鼠模型,将18只裸鼠随机等分为3组,生理盐水组、Mel组和顺铂组。观察各组裸鼠骨肉瘤的体积和体质量抑制率;应用免疫组织化学法检测各组裸鼠瘤体 CD31、CD105、PCNA 蛋白表达;应用TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究Mel抑制骨肉瘤血管生成与细胞增殖、凋亡的关系。结果 Mel组肿瘤体积和体质量抑制率分别为42.98%和39.03%,Mel能明显抑制CD31、CD105标记的血管生成密度,能明显抑制肿瘤细胞增殖,促进细胞凋亡,且Mel抑制肿瘤血管生成与细胞增殖呈正相关及与细胞凋亡呈负相关。结论 Mel具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成、诱导肿瘤细胞凋亡及抑制细胞增殖有关。

The relation of inhibiting angiogenesis and inducing cell apoptosis of melittin(Mel) on xenotransplanted models of nude mice

Objective To study the antitumor effects and mechanism of melittin(Mel) on xenotransplanted models of nude mice.Methods Xenotransplanted models of SD rat osteosarcoma(OS) cell UMR-106 in the laevo-hind tibia of nude mice were established.Eighteen inoculated mice were randomly divided into normal saline group,positive control group and Mel group.All the nude mice were sacrificed after treatment.The size and weight of tumor were measured and the tumor volumes,and the inhibition rates of tumor were calculated.The expressions of CD31,CD105 and PCNA were deteced by immunohistochemical method.TUNEL semi-quantitative assay was used to study the melittin-induced apoptosis in OS cell line.The relation of inhibiting angiogenesis and inducing cell apoptosis was analyzed by correlation test.Results The mice treated with Mel showed significantly smaller in tumor volume and weight than those of NS group after treatment.Microvessel densities and the protein expressions of CD31,CD105 and PCNA in Mel group were significantly lower than those in NS group.After the treatment of melittin,the apoptotic index detected by TUNEL assay increased remarkably.Conclusions The mechanism of the inhibition of the implanted tumor growth treated with Mel may be associated with the inhibition of angiogenesis in transplanted tumor.Furthermore,Melittin can induce cell apoptosis.