In vitro Scolicidal Efficacy of 5-Fluorouracil and Radiation Against Protoscoleces of Echinococcus granulosus Sensu Lato.

Abstract

Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a globally distributed zoonosis. CE treatment is difficult, but radiation and 5-fluorouracil (5-FU) can be effective. However, the combination of radiation and 5-FU has not been reported. This study evaluated the effect of combination of 5-FU and radiation on E. granulosus s.l. protoscoleces (PSCs). In this study, PSCs were collected from the liver of diseased sheep, and some were exposed to a single dose of 20 Gy 6-MV X-ray combined with (5 μg/mL or 10 μg/mL) 5-FU in vitro. Methylene blue staining was used to detect the viability of the PSCs. Transcription of EgHSP70 and Egp38 was measured by quantitative real-time PCR (qRT- PCR). A single dose of radiation killed 18% of the PSCs, and 5-FU showed weak parasiticidal efficacy on the first day of treatment. After 14 d, 5 μg and 10 μg/mL of 5-FU killed 40.20% and 50.02% of the PSCs, whereas 20 Gy of radiation killed 31.44%. The combination of 5-FU (10 μg/mL) with 20 Gy of radiation showed 77.55% killing efficacy. qRT-PCR showed that 5-FU inhibited Egp38 expression, whereas radiation increased its expression. EgHSP70 was highly expressed 14 days after radiation treatment. The data indicate that 5-FU has parasiticidal efficacy against the PSCs of E. granulosus s.l. The lethal efficacy of PSCs caused by a single dose of radiation exposure is related to the upregulated expression level of Egp38 and EgHSP70. The killing effect of 5-FU (10 μg/mL) with 20Gy of radiation was significantly better than that of single treatment group. This study provided a basis for the potential role of 5-FU combined with radiation in the treatment of CE.