Selective activity of BS-RNase against anaplastic thyroid cancer

Background. Anaplastic thyroid carcinoma is an aggressive solid tumor that fails to adequately respond to any known chemotherapeutic regimen. The deve lopment of effective chemotherapy agents would provide the best chance for longterm survival of patients. Materials and Methods. The cytotoxic effects of bovine seminal ribonuclease (BS-RNase) against thyroid carcinoma cell l ines with different degrees of differentiation in comparison to non-maligna nt cells, including human foreskin fibroblasts (HFF) and retinal pigment ep ithelial cells (RPE), were tested using the MTT dye reduction assay Inducti on of apoptosis was demonstrated by annexin V assay and expression of prote ins related to apoptosis was investigated by flow cytometry. The antitumora l in vivo effects of BS-RNase were assessed on established xenografts of an aplastic thyroid carcinoma cell line 8505C in nude mice using subcutaneous injections of BS-RNase (12.5 mg/kg once a day, on 20 consecutive days). Res ults. All the tumor cell lines exhibited marked sensitivity against BS-RNas e in comparison to HFF and RPE cells. The greatest growth inhibition was se en in the 8505C line, while IC50 values for papillary (B-CPAP) and poorly-d ifferentiated thyroid carcinoma cells were about 6-fold higher. The cytotox ic action of BS-RNase was associated with induction of apoptosis. Expressio ns of Fas and Fas-ligand were not influenced by BS-RNase completely: while the down-regulation of Bcl-2 in treated cells was observed. In vivo treatme nt induced significant tumor regression after the course of 20 consecutive days. No apparent toxic effects of BS-RNase toward nonmalignant cells were observed during the in vivo treatment. After cessation of therapy (day 20) tumor volume continued to decrease and the tumor was no longer detectable a fter 30 dal's of treatment induction in all animals. Conclusion. BS-RNase m ay have beneficial effects for treatment of aggressive anaplastic thyroid c ancer.