Lidamycin inhibits tumor growth and pulmonary metastasis in murine breast carcinoma and shows synergy with paclitaxel  

作　　者：HU Lei ZHANG ShengHua SHAO RongGuang ZHEN YongSu 

机构地区：[1]Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Chinese Science Bulletin》2013年第23期2805-2811,共7页

基　　金：supported by the Significant New Drugs Development Science and Technology Major Projects of China(2010ZX09401-407);State-level Public Welfare Scientific Research Institutes for Basic R&D Special Fund(IMBF201101)

摘　　要：The main goal of this study was to investigate whether lidamycin (LDM) could enhance the efficacy of paclitaxel (TAX) against breast cancer. In the MTT assay, LDM showed much more potent cytotoxicity than paclitaxel, and there was a synergy on the 4T1/luc breast cancer cells treated with a combination of paclitaxel and LDM. Western blot analysis showed that paclitaxel and LDM synergistically downregulated MMP9, MMP2, VEGF, and upregulated the cleaved PARP proteins. By wound closure cell migration assay, paclitaxel combined LDM obviously inhibited the migration of 4T1/luc cells. At therapeutic dosage level, LDM, paclitaxel, and the combination suppressed the pulmonary metastases by 70.2%, 53.8%, and 88.7%, respectively, and the CDI value was 0.82, indicating synergism. The results show that LDM enhances the antitumor effect of paclitaxel on 4T1/luc breast cancer, in particular, the antimetastatic effects on pulmonary metastasis.The main goal of this study was to investigate whether lidamycin （LDM） could enhance the efficacy of paclitaxel （TAX） against breast cancer. In the MTF assay, LDM showed much more potent cytotoxicity than paclitaxel, and there was a synergy on the 4T1/luc breast cancer cells treated with a combination of paclitaxel and LDM. Western blot analysis showed that paclitaxel and LDM synergistically downregulated MMP9, MMP2, VEGF, and upregulated the cleaved PARP proteins. By wound closure cell migration assay, paclitaxel combined LDM obviously inhibited the migration of 4T1/luc cells. At therapeutic dosage level, LDM, paclitaxel, and the combination suppressed the pulmonary metastases by 70.2%, 53.8%, and 88.7%, respectively, and the CDI value was 0.82, indicating synergism. The results show that LDM enhances the antitumor effect of paclitaxel on 4T1/luc breast cancer, in particular, the antimetastatic effects on pulmonary metastasis.

关 键 词：血管内皮生长因子 乳腺癌细胞 协同作用 力达霉素 紫杉醇 抑制肿瘤 肺 小鼠 

分 类 号：R737.9[医药卫生—肿瘤]