Effect of Carboxylesterase Inhibition on the Anti-Tumour Effects of Irinotecan

Abstract

Irinotecan (CPT-11) is an important anticancer agent activated by carboxylesterase (CE). Treatment with CPT-11 may be associated with severe adverse effects, however, so determining the optimal dose would greatly benefit patients. We investigated the relationship between the anti-tumour effects of CPT-11 and CE concentration using bis- p-nitrophenylphosphate (BNPP), a specific inhibitor of CE, in nude mice with xenograft tumours. Initial experiments showed that the optimal dose of CPT-11 was 100 mg/kg. This dose was then used to study the anti-tumour effects of CPT-11 with and without BNPP. A direct correlation was found between the dose of administered BNPP and the growth rate of the tumour, demonstrating that the anti-tumour effects of CPT-11 were related to the CE concentration. Measuring the concentration of CE may allow the optimum dose of CPT-11 to be determined, opening up the possibility of individualized chemotherapy programmes.