病毒巨噬细胞炎性蛋白Ⅱ-N端肽联合三氧化二砷对乳腺癌生长和转移的抑制作用

Inhibitory Effects of Viral Macrophage Inflammatory ProteinⅡ-derived Synthetic Polypeptide and Arsenic Trioxide on Tumor Growth and Metastasis in Mouse Models of Breast Cancer

目的利用荷乳腺癌动物模型观察病毒巨噬细胞炎性蛋白Ⅱ-N端肽(NT21MP)联合三氧化二砷(As2O3)对乳腺癌生长和肺转移的抑制效应,为选择最佳的乳腺癌治疗方案提供依据。方法建立荷乳腺癌BALB/c小鼠模型,测量荷瘤小鼠的肿瘤大小,计算抑瘤率;苏木精-伊红(HE)染色观察肿瘤病理组织学变化和肺转移情况;苦味酸浸泡法计数肺结节;利用TUNEL法及免疫组化SP法检测各组原发肿瘤组织中细胞凋亡指数(AI)以及增殖细胞核抗原(PCNA)的表达。结果 NT21MP和As2O3均可抑制原发瘤的生长,抑制率分别为30.4%和40.0%,联合用药效果更显著(54.4%)。NT21MP和As2O3均可抑制肺转移,以两者联合用药作用更明显。与生理盐水对照组相比,NT21MP组、As2O3组及NT21MP+As2O3组增殖细胞核抗原指数明显降低(均P<0.05),凋亡指数明显升高(均P<0.05),以联合用药作用更明显(P<0.05)。结论 NT21MP和As2O3可通过抑制增殖、促进凋亡而抑制肿瘤的生长和转移,并具有协同效应。

Objective To investigate the inhibitory effect of combined treatment with a synthetic antagonist 21-mer peptide derived from viral macrophage inflammatory protein-Ⅱagainst CXCR4（NT21MP）and As2O3 on the growth and metastasis of breast cancer in an attempt to provide the optimal chemotherapeutic strategy for breast cancer.Methods The BALB/c mouse model of breast cancer was established.Animals were divided into 4groups：control group,NT21MP group,As2O3 group and NT21MP＋As2O3 group.The tumor weight was measured and tumor inhibition rate calculated.The pathological changes of primary tumors and the pulmonary metastasis were observed by using hematoxylin eosin（HE）staining.Metastatic lung nodes were counted by using Bouin fixation.The apoptosis index（AI）of primary cancer cells and the expression of PCNA in primary cancer tissues were detected by TUNEL and immunohistochemistry（SP method）respectively.Results Either NT21MP or As2O3 could inhibit the growth of the primary tumor and the inhibition rate was 30.4%and 40.0% respectively.The inhibitory effect was most significant in the combination group with the tumor inhibition rate reaching 54.4%.Administration with NT21MP and As2O3 combined could substantially inhibit the pulmonary metastasis when compared with treatment with NT21MP or As2O3 alone.The expression of PCNA was significantly decreased and the AI obviously increased in primary tumors in NT21MP group,As2O3 group and NT21MP＋As2O3 group relative to the saline control group（P〈0.05）.Conclusion NT21MP and As2O3 can synergically inhibit the growth and metastasis of breast cancer by inhibiting proliferation and inducing apoptosis.