Low-dose SN-38 with paclitaxel induces lethality in human uterine cervical adenocarcinoma cells by increasing caspase activity

Combination of anticancer drugs may provide a rational molecular basis for novel chemotherapeutic strategies. Paclitaxeland SN-38(an active metaboliteof CPT-11) are effective for many kinds of cancer. Therefore, we investigated the possibility that combination of these drugs could be effective against cervical adenocarcinomacells. In this study, we examined cell growth inhibition after 96 h using the MTT assayand examined the release of fragmented DNA into the cytoplasm during apoptotic cell death by PI staining. Single and combined use of paclitaxeland SN-38produced significant cytolethality against the cervical adenocarcinomacell line CAC-1. Addition of a low concentration of SN-38reduced the IC50 value of paclitaxelcompared to that without SN-38, although the low concentration of paclitaxeldid not enhance the cytotoxicity of SN-38. FACS scan analysis suggested that these drugs induced apoptosis and cell cycle arrest, and that caspase-3 and -7 were activated in the process. MTT assayand the IC50 demonstrated that paclitaxelhad strong cytotoxicity against CAC-1 as well as other cancer cells. In this study, though only a single cell line was used for the experiment and the data are limited, our results suggest that paclitaxeltogether with low-dose CPT-11 is a promising basis for a new combination cancer chemotherapy.