In vitro inhibitive effect of the anticancer drug sorafenib on Echinococcus multilocularis larvae

Abstract

Abstract:

Objective To evaluate the effect of an anti-cancer drug sorafenib against alveolar echinococcosis (AE) in vitro. Methods Metacestode vesicles were obtained from infected mice and cultured with rat hepatocytes in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal calf serum (FCS), 100 U/ml penicillin G and 100 mg/L streptomycin sulphate at 37 ℃ with 5% CO₂. Morphologically intact metacestode vesicles with a minimal diameter of 2-4 mm were manually picked up from the co-culture and washed with PBS. They were then allocated (n = 25-30 cysts/well) into four groups: albendazole-treated group (positive group), sorafenib-treated group (experimental group), DMSO-treated group (solvent group), and PBS group (negative control), and incubated in 24-well plates in the presence of DMEM without phenol red. Albendazole and sorafenib were dissolved in DMSO (1 ∶ 9 dissolved in PBS) and used at 10 μmol/L and 30 μmol/L respectively. The experiment was performed in triplicates per sample. The integrity of the cysts was assessed with light microscopy and scanning electron microscopy (SEM). The inhibitory effects of albendazole and sorafenib on cysts were evaluated at 48, 72, 96, 120, 144 and 168 h post-treatment. Results The cyst inhibitory rate of sorafenib was 6.6%, 42.4%, 68.5%, 77.4%, 84.0% and 89.5% at 10 μmol/L, and 7.1%, 45.6%, 70.9%, 82.6%, 84.0% and 89.9% at 30 μmol/L, respectively, at 48, 72, 96, 120, 144 and 168 h post-treatment. While the cyst inhibitory rate of albendazole was 2.6%, 6.6%, 21.4%, 47.8%, 59.9% and 70.6% at 10 μmol/L, and 3.8%, 12.7%, 27.0%, 51.4%, 54.0% and 73.0% at 30 μmol/L, respectively. DMSO and PBS showed less toxic to the cysts. Sorafenib exerted a stronger inhibitory effect than albendazole at the corresponding time points, and the difference began to be statistically significant from 72 h post-treatment. Light microscopy and SEM showed observable collapse of the germinal layer and overall damage of germinal cells in the experiment groups. Conclusion Sorafenib shows a significant inhibitory effect on Echinococcus cysts, suggesting a potential drug candidate for echinococcosis treatment.

Key words: Alveolar echinococcosis, Germinal layer, Sorafenib

CLC Number:

R383.33

Zhi-sheng DANG, Yuzaburo OKU, Xiao-nong ZHOU, Wei HU, Ting ZHANG, Jun-hu CHEN, Bin XU, Yu-min ZHAO, Ning XIAO. In vitro inhibitive effect of the anticancer drug sorafenib on Echinococcus multilocularis larvae[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2017, 35(5): 417-422.

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