Fascaplysin抑制ICR小鼠体内S180移植瘤的分子机制初探

Preliminary Study on Anti-tumor Mechanism of Fascaplysin on Sarcoma Mice Model

目的研究fascaplysin对ICR小鼠S180移植瘤生长的体内抑制作用,并初步探讨fascaplysin在体内抑瘤的分子机制。方法皮下注射技术建立荷S180骨肉瘤的ICR小鼠为实体瘤动物模型,然后将其分为4组:即空白对照组(注射生理盐水)、阳性对照组[CTX,30mg/(kg.d)]、fascaplysin高剂量组[20mg/(kg.d)]和fascaplysin低剂量组[5mg/(kg.d)],处理10天后,利用电镜分析各组小鼠移植瘤细胞的变化,应用免疫组化技术检测相应组织PCNA、CD31表达情况。结果电镜结果显示肿瘤组织细胞出现凋亡现象。PCNA结果发现,fascaplysin治疗组与空白对照组相比差异极显著(P<0.01),高、低剂量组之间差异显著(P<0.05),具有一定程度的剂量-效应依赖性。MVD结果:与空白对照组相比,fascaplysin各剂量组肿瘤组织内MVD均明显减少(P<0.01)。结论 Fascaplysin治疗能诱导肿瘤细胞凋亡,减少肿瘤组织PCNA的表达,降低肿瘤的增殖活性。减少肿瘤组织微血管的密度,抑制肿瘤血管的新生。提示fascaplysin在体内具有良好的抗肿瘤作用。

Objective To study the inhibitory effects of fascaplysin on the growth of S180 transplanted tumor in ICR mice, and to explore the anti - tumor mechanism of fascaplysin in vivo. Methods A sarcoma mice model was established, and the mice were divided into four groups, including control group （ injected with 0.9% NaC1）, positive group [ injected with 30rag/（ kg . d） cyclophosphamide], high dose group [ received 20mg/（ kg . d） fascaplysin], and low dose group [ 5mg/（ kg.d） fascaplysin ]. After treated with fascaplysin for 10 days, the tumor tissues were examined morphologically by transmission electron microscope. Tissue sections were also immunostained with monoclonal antibody directed to proliferating cell nuclear antigen （PCNA） and CD31 to detect the proliferating activity of tumor cells and the distribution of micro vessels. Results Typical apoptotic phenomena were observed by transmission electron microscope. Immunohistochemical test results showed that the expression of PCNA in the two fascaplysin groups was decreased significantly compared with that of the blank control （P 〈 0.01 ）. And the difference between the low dose group and high dose group was also significant （ P 〈 0. 05 ）, which indicated that Fascaplysin decreased the expression of PCNA in S180 transplanted tumor of ICR mice in a dose - effect dependent manner. Microvessel density （MVD） assay indicated that the MVD in the two Fascaplysin groups was decreased significantly compared with that of the blank control, P 〈 0.01. Conclusion From these findings, it can be considered that fascaplysin can inhibit the growth of S180 cell implanted tumor, and the action mechanisms may involve in apoptosis and anti angiogenesis.