Cisplatin augments the anti-schistosomal effect of praziquantel in a schistosoma-infected cancer model

Abstract

Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. Tumor burden can be developed in Schistosoma-infected patients. The present study aimed to determine the host responses to mutual interaction between cancer, represented by Ehrlich ascites, and infection, represented by Schistosomiasis. Mice infected with Schistosoma and challenged with tumor 4-5 weeks later showed the same anti-schistosomal (worm and egg burden) and antitumor (total tumor cell count and mouse survival) parameters when compared to mice infected with Schistosoma alone or challenged with tumor cells alone. As expected, combinatorial treatment with PZQ and cisplatin of Schistosoma-infected mice that were challenged with tumor cell line decreased the tumor burden as well as the worm and egg burden after treatment as compared to the non-treated controls; while the worm burden and egg counts were significantly decreased (P <0.001) in treated group (VI) treated with cisplatin (0.5 mg/kg), group (VII) treated with cisplatin (2 mg/kg), group (VIII) treated with PZQ/ cisplatin (0.5 mg/kg) and group (IX) treated with PZQ / cisplatin (2 mg/kg) by 44.55% , 74%, 100% and 97.8% in worm burden, and by 47%, 78.7%, 96% and 97% in liver egg count , respectively than that of group (II) non treated S. mansoni infected alone and (IV) non treated S. mansoni/EAC alone. Also, Group IX caused a significant reduction (P <0.05) in worm burden than that of group VI. Also, total ascetic volume and the tumor cell counts in Ehrlich's ascites carcinoma (EAC)-cells were significantly decreased (P <0.001) in groups VIII and IX than that of the group (III) non-treated (EAC) inoculated alone. There was no mutual interaction between schistosomiasis infection and tumor burden. Also, whereas, PZQ did not affect on the antitumor parameters, cisplatin even at low doses had anti-schistosomal effects.