多西紫杉醇单独或与巴马司他联合应用抗小鼠前胃癌转移的作用(英文)

Effects of docetaxel alone or in combination with batimastat against metastasis of mouse forestomach carcinoma 1

研究细胞毒新药多西紫杉醇和第一个进入临床试验的金属蛋白酶抑制剂巴马司他 (BB- 94)单独或联合应用对小鼠前胃癌 (MFC)的抗转移作用 ,并与多柔比星做比较 .体外侵袭实验表明 :多西紫杉醇和 BB- 94均能抑制 MFC细胞侵袭并穿过重组基底膜的能力 ,而且 BB- 94可增强多西紫杉醇的这种作用 .多西紫杉醇还可抑制 MFC细胞在层粘连蛋白上的粘附作用 .体内实验表明 ,给予最大耐受剂量多西紫杉醇 (2 0 mg· kg-1)或多柔比星 (6mg·kg-1iv,每 4d1次 ,共计 3次 )和 BB- 94(30 mg·kg-1,ip,每日 1次 ,连续 2 0 d)均具有明显的抗肿瘤转移作用 .多西紫杉醇联用 BB- 94对肺转移灶的抑制率大于多柔比星联用 BB- 94,多西紫杉醇 ,多柔比星和 BB- 94,而且 BB- 94可明显增强多西紫杉醇的抗肿瘤转移作用 .

The combined antimetastatic effect of docetaxel, a new cytotoxic agent, and batimastat (BB-94), the first matrix metalloproteinase inhibitor in clinical trial, was studied on mouse forestomach carcinoma (MFC), as compared with doxorubicin. In vitro, docetaxel (10-100 nmol·L -1) or BB-94 (50-500 nmol·L -1) could inhibit chemoinvasion of MFC cells in Boyden chamber invasion study, and anti-invasive activity of doceta- xel could be enhanced by BB-94. The reduced adhesion of MFC cells to laminin by docetaxel (10-500 nmol·L -1) might be one of the mechanisms related to its effect. In vivo, obvious antimetastatic effect of docetaxel or doxorubicin given iv at maximum tolerated dose (docetaxel 20 mg·kg -1, doxorubicin 6 mg·kg -1) every 4 d for 3 injections, and of BB-94 (30 mg·kg -1, ip, once a day for 20 d) was observed. The inhibition rates of lung total metastatic foci and large foci (>3 mm in diameter) were greater for docetaxel-BB-94 combination (74.0% and 91.0%) than doxorubicin-BB-94 (51.6% and 44.8%), docetaxel (42.0% and 49.8%), doxorubicin (19.2% and 15.9%) and BB-94 (33.0% and 40.8%). Therefore the results suggest that BB-94 enhance the antimetastatic activity of docetaxel in MFC tumor model.