来源于HHV8 MIP N端多肽抗乳腺癌作用的实验研究

Role of NT21MP from HHV8 MIP N-terminal peptide in resisting breast cancer

目的:探讨来源于HHV8MIPN端多肽(NT21MP)治疗小鼠乳腺癌的疗效。方法:采用乳腺癌细胞株4T-1构建乳腺癌小鼠模型;实验分为NT21MP5μg/kg、50μg/kg和500μg/kg组,NT21MP与Herceptin联合用约组(NT21MP50μg/kg+Herceptin36.04μg/kg)、阳性对照组(Herceptin36.04μg/kg)及生理盐水对照组;观察各组小鼠肿瘤体积大小,并计算抑瘤率;检测肺转移结节。结果:与生理盐水组荷瘤小鼠比较,NT21MP呈剂量依赖性地抑制肿瘤的生长,以联合用药组为明显(P<0.01)。NT21MP不同浓度、联合用药及阳性对照组的抑瘤率分别为10.0%、41.6%、81.0%、58.2%及39.2%;对照组小鼠肺内均见转移性Lewis肺癌瘤灶,肺脏表面可见多个肿瘤转移结节;NT21MP5μg/kg组小鼠肺内均见转移性Lewis肺癌瘤灶,肺脏表面可见到散在的肿瘤转移结节;NT21MP50μg/kg组和Herceptin组中,各有5/6动物肺内见转移性Lewis肺癌瘤灶,肺表面可见小的单个肿瘤转移结节;NT21MP500μg/kg组和联合用药组各有2/6和3/6动物肺内见转移性Lewis肺癌瘤灶,肺表面未见明显的转移结节。结论:NT21MP可抑制乳腺癌的生长和转移,联合应用基因靶向药物Herceptin,可提高对乳腺癌靶向治疗的效果。

Objective：To investigate the function of NT21MP from human herpesvirus-8 （HHV8） monocyte inflammatory protein （MIP） N-terminal peptide in resisting breast cancer. Methods： Breast carcinoma model mice were established by 4T-1 breast cancer cell strains. The models were divided into NT21MP group （5 μg/kg, 50 μg/kg and 500 μg/kg） , combination therapy group （NT21MP 50 μg/kg ＋ Hereeptin 36.04 μg/kg） , positive control group（ Herceptin 36.04 μg/kg） and sodium chloride group. The size of the tumor on the tumor-bearing mice was observed, the tumor inhibitory rate was calculated and the metastasis lung node was detected. Results：Compared with the tumor-bearing mice in sodium chloride group, NT21MP inhibited the growth of tumor in a dose-dependent manner,which was the most evident in the combination group（P 〈 0.01 ）. The tumor inhibitory rates in the NT21MP groups with different concentrations,the combination group and the positive control group were 10： 0% ,41 6% , 81.0% , 58.2% and 39.2% respectively. Metastasis Lewis lung cancers were observed in both of the control groups, and several metastasis nodes of white tumor were observed on the surface of the mice＇s lung; and the situation was the same with NT21MP 5 μg/kg group. In NT21MP 50 μg/kg group and Herceptin group, metastasis Lewis lung cancers were noted in the lungs of five sixths of the mice, and small and single metastasis node was found on the surface of the lung. In the NT21MP 500 μg/kg group and the combination therapy group,metastasis Lewis lung cancers were noted in two sixths and three sixths of the mice, respectively, and no obvious metastasis nodes were found on the surface of the mice＇s lung. Conclusions： NT21MP may inhibit the growth and metastasis of breast cancer. Combination therapy of NT21MP and the targeted drug Herceptin can improve the clinical efficacy.