Senter P D, Marquardt H, Thomas B A, Hammock B D, Frank I S, Svensson H P
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Cancer Res. 1996 Apr 1;56(7):1471-4.
Paclitaxel-2-ethylcarbonate (PC) is a prototype for a family of paclitaxel prodrugs that have significant levels of antitumor activities in rodent models for human cancer. In this study, an enzyme responsible for the conversion of PC to paclitaxel was purified from rat serum. N-terminal amino acid sequence analysis indicated that the isolated enzyme was rat serum carboxylesterase. This enzyme was shown to significantly enhance the cytotoxic activities of both PC and 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a water-soluble analogue of camptothecin, on lung carcinoma and melanoma cell lines. Rat serum carboxylesterase may have applications for the site-specific delivery of anticancer drugs to tumor masses.
紫杉醇-2-碳酸乙酯（PC）是一类紫杉醇前体药物的原型，这类前体药物在人类癌症的啮齿动物模型中具有显著水平的抗肿瘤活性。在本研究中，从大鼠血清中纯化出一种负责将PC转化为紫杉醇的酶。N端氨基酸序列分析表明，分离出的酶是大鼠血清羧酸酯酶。该酶被证明能显著增强PC和7-乙基-10-[4-(1-哌啶基)-1-哌啶基]羰氧基喜树碱（CPT-11，喜树碱的水溶性类似物）对肺癌和黑色素瘤细胞系的细胞毒活性。大鼠血清羧酸酯酶可能在将抗癌药物位点特异性递送至肿瘤块方面具有应用价值。
