抗人IgM抗体抑制人鼻咽癌细胞株HNE-1细胞裸鼠移植瘤生长机制

Mechanism of anti-human IgM antibody on the growth inhibition of human nasopharyngeal carcinoma HNE-1 cell xenograft in nude mice

目的观察抗人IgM抗体作用于人鼻咽癌H N E-1裸鼠移植瘤生存素(Su r v iv i n)、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、血管生成素-2(angiopoietin-2,Ang-2)及移植瘤内微血管密度(microvessel density,MVD)表达变化情况,探讨IgM抗体抑制人鼻咽癌细胞株HNE-1细胞裸鼠移植瘤生长可能的作用机制。方法应用免疫组化SABC法检测移植瘤组织中Survivin、PCNA、Ang-2表达情况,免疫组化SAP法检测CD31标记的移植瘤内微血管并计数MVD。结果①实验组Survivin、PCNA、Ang-2阳性表达的结果显著低于IgG对照组和PBS对照组,差异有统计学意义;②实验组MVD为12.54±0.47,显著低于IgG对照组(16.95±0.21)及PBS对照组(17.17±0.47),差异有统计学意义;③HNE-1细胞裸鼠移植瘤组织中MVD分别与Survivin和Ang-2呈显著正相关关系(r分别为0.754、0.696,P均<0.05)。结论①抗人IgM抗体可以显著抑制HNE-1细胞裸鼠移植瘤组织内Survivin、PCNA、Ang-2的表达;②抗人IgM抗体可以显著抑制HNE-1细胞裸鼠移植瘤组织MVD,其机制可能与抑制Ang-2、Survivin的表达有关;③抗人IgM抗体抑制HNE-1细胞裸鼠移植瘤生长的机制可能与其抑制Survivin、PCNA、Ang-2的表达,促进凋亡、抑制细胞增殖和血管生成有关。

OBJECTIVE To observe the changes of survivin, proliferating cell nuclear antigen （PCNA）, angiopoietin-2 （Ang-2） and microvessel density （MVD） in human nasopharyngeal carcinoma（NPC） HNE-1 cell xenograft in nude mice after treated with Anti-human immunoglobulin（Ig） M antibodies, and to explore the possible mechanism of anti-human IgM antibodies inhibiting the growth of human NPC HNE-1 cell xenograft in nude mice. METHODS The expression of survivin, PCNA, Ang-2 were measured by immunohistochemical Streptoavidin-biotin-enzyme Complex （SABC） method, the expression of tumor microvessel marked with CD31 were detected by immunohistochemical streptavidin-Alkaline Phosphatase （SAP） method, and MVD was counted. RESULTS 1. Positive expression of survivin, PCNA and Ang-2 in the experimental group were significantly lower than those in the IgG control group and PBS control group, the difference was statistically significant （P〈0.05）. 2.The MVD value of anti-human IgM antibody treatment group was （12.54± 0.47）, significantly lower than that of IgG control group （16.95±0.21） and PBS control group （17.17±0.47）, the difference was statistically significant （P〈0.05）. 3.The MVD was positively correlated with the expression of survivin and Ang-2 protein in xenograft tissues of human NPC HNE-1 cell in nude mice （r=0.754, 0.696 respectively, P=0.001, 0.004 respectively）. CONCLUSION 1.Anti-human IgM antibody can significantly inhibit the expression of survivin, PCNA and Ang-2 in xenograft tissues of human NPC HNE-1 cell in nude mice. 2.Anti-human IgM antibody can significantly inhibit the expression of microvessel （MVD）/angiogenesis in oxenograft tissues of human NPC HNE-1 cell in nude mice. The mechanism may be related to the inhibition of Ang-2 and survivin expression. 3. The mechanism of Anti-human IgM antibody on the growth inhibition of human NPC HNE-1 cell xenograft in nude mice may be related to the promotion of apoptosis and the inhibition of cell proliferation and angiogenesis by reduction of the expression of survivin, PCNA and Ang-2.