目的了解基质金属蛋白酶抑制剂对肝癌生长和侵袭转移的影响及其机制。方法通过腹腔注射BB-94对二乙基亚硝胺建立的大鼠原发性肝癌模型进行治疗,观察BB-94对肝癌的生长和侵袭转移的抑制作用,并应用明胶酶谱法研究BB-94治疗后基质MMP-2和M...目的了解基质金属蛋白酶抑制剂对肝癌生长和侵袭转移的影响及其机制。方法通过腹腔注射BB-94对二乙基亚硝胺建立的大鼠原发性肝癌模型进行治疗,观察BB-94对肝癌的生长和侵袭转移的抑制作用,并应用明胶酶谱法研究BB-94治疗后基质MMP-2和MMP-9的表达情况及对其活性形式的影响;探讨BB-94影响肝癌生长和侵袭转移的机制。结果 BB-94对肿瘤生长、侵袭转移均有明显的抑制作用,治疗组与对照组肝脏肿瘤质量为(3.6±0.4)g vs(4.1±0.4)g(P<0.001);并能延长其生存期;对酶原形式的MMP-2和MMP-9无影响,而使MMP-2活性形式的表达量显著降低,治疗组和对照组分别为28.5±19.8 vs 42.8±20.1(P<0.05)。结论BB-94可通过降低活性形式MMP-2的表达来抑制肝细胞癌的生长和侵袭转移。展开更多
Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vit...Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg) every 4 days for 3 injections (q4d×3), even that of BB 94 (30mg/kg i.p. qd×20) was observed. Tumor growth inhibition was greater for docetaxel batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB 94 (33.0%), and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.展开更多
文摘目的了解基质金属蛋白酶抑制剂对肝癌生长和侵袭转移的影响及其机制。方法通过腹腔注射BB-94对二乙基亚硝胺建立的大鼠原发性肝癌模型进行治疗,观察BB-94对肝癌的生长和侵袭转移的抑制作用,并应用明胶酶谱法研究BB-94治疗后基质MMP-2和MMP-9的表达情况及对其活性形式的影响;探讨BB-94影响肝癌生长和侵袭转移的机制。结果 BB-94对肿瘤生长、侵袭转移均有明显的抑制作用,治疗组与对照组肝脏肿瘤质量为(3.6±0.4)g vs(4.1±0.4)g(P<0.001);并能延长其生存期;对酶原形式的MMP-2和MMP-9无影响,而使MMP-2活性形式的表达量显著降低,治疗组和对照组分别为28.5±19.8 vs 42.8±20.1(P<0.05)。结论BB-94可通过降低活性形式MMP-2的表达来抑制肝细胞癌的生长和侵袭转移。
文摘Objective . To improve the treatment of tumors, we studied the combined effects of docetaxel and batimastat (BB 94) on mouse forestomach carcinoma (MFC), and compared them with doxorubicin. Methods and results. In vitro, growth curve analysis, MTT assay and clonogenic assay used to determine the cytotoxic effect of docetaxel or/and BB 94 on MFC cell showed that docetaxel but not BB 94 had a significant cytotoxicity, and the effect of docetaxel wasn’t enhanced by BB 94. In early stage MFC tumor model, obvious antitumor effect of docetaxel or doxorubicin given i.v. at maximum tolerated dose (MTD, docetaxel: 20mg/kg; doxorubicin: 6mg/kg) every 4 days for 3 injections (q4d×3), even that of BB 94 (30mg/kg i.p. qd×20) was observed. Tumor growth inhibition was greater for docetaxel batimastat (96.0%) than for doxorubicin-batimastat (88.0%), docetaxel (89.0%), doxorubicin (68.0%) and BB 94 (33.0%), and the effect of docetaxel could be potentiated by BB 94. Docetaxel also showed activity against advanced stage MFC tumor in dose-dependent manner, and was more effective at MTD than doxorubicin with 4/5 regressions, 46.5 days tumor growth delay and 2.8log10 tumor cell kill. Conclusion. Our results suggest that in the MFC model with dose and schedule used, docetaxel is an effective cytotoxic new drug against MFC tumor and BB 94 enchances the antitumor activity of docetaxel.
