乳癌术后方对HER2阳性乳腺癌复发转移中基质金属蛋白酶及其抑制因子的影响  

Effects of Ru′ai Shuhou Recipe on the Matrix Metalloproteinases and the Inhibitive Factors in the Recurrence and Metastasis of HER2 Positive Breast Cancer

作　　者：吴雪卿[1] 邵士珺[1] 瞿文超[1] 冯佳梅[1] 高晴倩[1] 张婷婷[1] 万华[1] 

机构地区：[1]上海中医药大学附属曙光医院乳腺科,上海200021

出　　处：《中国中西医结合杂志》2012年第11期1526-1530,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：上海市自然科学基金项目资助(No.09ZR1432500)

摘　　要：目的观察乳癌术后方抗HER2阳性乳腺癌复发转移的疗效,评估该方对HER2阳性乳腺癌复发转移过程中基质金属蛋白酶及其抑制因子的影响,揭示其抗复发转移的作用机制。方法选用30周龄左右发瘤相当的人类表皮生长因子受体2(HER2/neu)转基因自发乳腺癌小鼠FVB/neu,行原发肿瘤切除术,术后随机分为空白对照组、乳癌术后方组、赫塞汀组、联合用药组(乳癌术后方加赫赛汀),给药治疗4个月,评价复发肿瘤瘤积抑制率及肺转移抑制率;Western blot法检测治疗结束后各组小鼠复发肿瘤组织中基质金属蛋白酶-2、9(matrix metalloproteinase,MMP-2,9)及金属蛋白酶组织抑制因子-1、2(tissue inhibitor of metallo-proteinase,TIMP-1,2)的表达情况。结果治疗结束时空白对照组平均瘤积为(11.11±8.71)cm3,乳癌术后方组为(5.56±5.55)cm3,组间比较差异有统计学意义(P=0.037);空白对照组平均肺转移结节数为16个,乳癌术后方组为10个,乳癌术后方组肺转移抑制率达37.85%,但差异无统计学意义。乳癌术后方组活化的基质金属蛋白酶2(active-MMP2)表达较空白对照组、赫赛汀组及联合用药组均下调(P<0.05);3个用药组MMP9的表达水平较空白对照组下调(P<0.05),乳癌术后方组及联合用药组较赫赛汀组进一步下调(P<0.05);3个用药组TIMP-1、TIMP-2的表达均较空白对照组上调(P<0.05),其中乳癌术后方组与联合用药组TIMP-1表达的增加较赫赛汀组更为显著(P<0.05),赫赛汀组TIMP-2表达的增加较其余两个用药组更加显著,联合用药组高于乳癌术后方组(P<0.05)。结论乳癌术后方对FVB/neu小鼠术后乳腺肿瘤复发具有抑制作用;能够减少细胞外基质的降解,增加对细胞外基质的保护作用,通过影响乳腺肿瘤细胞浸润转移的能力发挥抗复发转移作用。Objective To observe the anti-tumor recurrent and metastatic efficacy of Ru′ai Shuhou Recipe （RSR） on HER2 positive breast cancer, to evaluate the effects of RSR on the expressions of matrix metalloproteinases （MMPs） and the tissue inhibitor of metalloproteinases （TIMPs） in the recurrence and metastasis of HER2 positive breast cancer, thus revealing its anti-tumor recurrent and metastatic mechanisms. Methods Selected were 30-week-old HER2/neu transgenic spontaneous breast cancer mice FVB/neu. The primary tumor resection was carried out. After surgery they were randomly divided into the blank control group, the RSR group, the Herceptin group, and the combination group （RSR＋Herceptin group）. The treatment lasted for 4 months. The inhibition rate of the recurrent tumor volume and the inhibition rate of the lung metastasis were evaluated. The expressions of matrix metalloproteinase-2 （MMP-2）, matrix metalloproteinase-9 （MMP-9）, tissue inhibitor of metalloproteinase （TIMP-1）, and TIMP-2 in the recurrent tumor tissue were detected using Western blot. ResultsBy the end of the treatment the average recurrent tumor volume was 11.11±8.71 cm3 in the blank control group and 5.56±5.55 cm3 of the RSR group, showing statistical difference between the two groups （P=0.037）. The average lung metastatic nodule was 16 in the blank control group and 10 in the RSR group. The inhibition rate of lung metastasis was 37.85% in the RSR group, but with no statistical significance. The expression level of activated MMP-2 in the RSR group was down-regulated when compared with the blank control group, the Herceptin group, and the combination group （P0.05）.The expression of MMP-9 of the RSR group, the Herceptin group, and the combination group was significantly down-regulated when compared with the blank control group （P0.05）. The expression of MMP-9 of the RSR group and the combination group was further down-regulated when compared with the Herceptin group （P0.05）. The expressions of both TIMP-

关 键 词：HER2阳性乳腺癌 基质金属蛋白酶-2、9 基质金属蛋白酶组织抑制因子-1、2 中药复方 

分 类 号：R737.9[医药卫生—肿瘤] R285.5[医药卫生—临床医学]