活性碳吸附丝裂霉素局部给药治疗腋淋巴结阳性乳腺癌模型的疗效研究

Local administration of activated carbon-adsorbed mitomycin C in treatment of breast cancermodel with metastasized axillary lymph nodes

目的:研究丝裂霉素-活性碳混悬液(MMC-CH)局部注射给药对腋淋巴结阳性的兔乳腺癌模型的治疗效果。方法:30只雌性新西兰兔随机分为三组,每组10只,VX2肿瘤组织块悬液注射法建立乳腺癌模型,腋淋巴结最大径达到5mm时开始治疗。A组:肿瘤周围皮下注射MMC-CH;B组:肿瘤周围皮下注射丝裂霉素水溶剂(MMC-Sol);C组:注射生理盐水。A、B组单次药物剂量0·2mg/kg,每48h重复给药1次,3次治疗后切除淋巴结。比较治疗前后淋巴结体积变化,病理切片观察转移灶癌组织坏死,dTUP末端标记技术(TUNEL)检测癌细胞凋亡指数(AI),组间差异比较采用ANOVA-Dunnett检验。结果:与MMC-Sol相比,局部注射MMC-CH对腋淋巴结癌转移灶表现出更为显著的疗效。治疗后A、B、C组淋巴结平均生长率分别为2·645、3·175和3·518,A组显著低于B、C组(P值分别为0·012和0·000)。A、B、C组平均AI值分别为15·94%、5·18%和4·60%,A组显著高于B组(P=0·000),B组又显著高于C组(P=0·020)。病理检查发现,A组淋巴结转移癌细胞大量坏死。结论:局部注射MMC-CH可有效治疗兔VX2乳腺癌区域淋巴组织转移。

OBJECTIVE: To investigate the therapeutic effect against tumor-involved axillary lymph nodes in rabbits bearing breast carcinoma with local administration of mitomycin C bound to activated carbon particles (MMC-CH). METHODS: Thirty female New Zealand white rabbits were divided into 3 groups randomly, with 10 in each. Breast carcinoma models were established by injecting VX2 tumor mass suspensions into the mammary gland of the rabbits. Treatment initiated once the axillary lymph node enlarged and attained 5 mm in the maximum diameter. Animals of Group A received a subcutaneous injection of MMC-CH adjacent to the implanted tumor. Group B received mitomycin C solution (MMC-Sol) and Group C received normal saline. The dose of mitomycin C was 0.2 mg/kg in Group A and Group B. The treatment was repeated every 48 hours. Axillary nodes were dissected after the third treatment. The therapeutic effects were compared in terms of the node volume ratio, necrosis and apoplosis of metastatic tumor cells in axillary nodes. The significance of differences was determined by ANOVA and Dunnett test. RESULTS: Compared with rabbits receiving MMC-Sol, a more apparent antitumor efficacy on metastasized nodes was observed in rabbits receiving subcutaneous injection of MMC-CH. After the treatment, the mean growth rates of nodes in Group A, B, and C were 2.645, 3.175, and 3.518, respectively. The differences between Group A and Group B or C were statistically significant (P=0.012 and P=0.000, respectively). The apoplotic indexes (AIs) in Group A, B, and C were 15.94%, 5.18%, and 4.60%, respectively. Significant difference was found between Group A and Group B (P=0.000), or Group B and C (P=0.02). Pathological examination revealed extensive necrosis of metastatic tumor cells in nodes of Group A. CONCLUSION: Local administration of MMC-CH appears to hold promising potential for the treatment of lymphatic metastases in rabbits bearing VX2 breast carcinoma.