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Abstract
BackgroundIdentification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has particularly important implications. In fact, the efficacy of the chemotherapeutic agents presently used in these tumours, is strongly limited by their low therapeutic index.MethodsIn this study gemcitabine was entrapped within a pegylated liposomal delivery system to improve the drug antitumoral activity, thus exploiting the possibility to reduce doses to be administered in cancer therapy. The cytotoxic effects of free or liposome-entrapped gemcitabine was evaluated against a human thyroid tumour cell line. ARO cells, derived from a thyroid anaplastic carcinoma, were exposed to different concentrations of the drug. Liposomes formulations were made up of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-MPEG (8:3:1 molar ratio). Cell viability was assessed by both trypan bleu dye exclusion assay and fluorimetric analysis of cell DNA content.ResultsA cytotoxic effect of free gemcitabine was present only after 72 h incubation (ARO cell mortality increased of approximately 4 fold over control at 1 μM, 7 fold at 100 μM). When gemcitabine was encapsulated in liposomes, a significant effect was observed by using lower concentrations of the drug (increased cell mortality of 2.4 fold vs. control at 0.3 μM) and earlier exposure time (24 h).ConclusionThese findings show that, in vitro against human thyroid cancer cells, the gemcitabine incorporation within liposomes enhances the drug cytotoxic effect with respect to free gemcitabine, thus suggesting a more effective drug uptake inside the cells. This may allow the use of new formulations with lower dosages (side effect free) for the treatment of anaplastic human thyroid tumours.
Highlights
Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has important implications
A major limit of the chemotherapeutic agents presently used in these tumours, including doxorubicin, paclitaxel and various drug combinations [1,2], is represented by their low therapeutic index
Our data demonstrate that incorporation of gemcitabine in liposomes enhances the cytotoxic effect of the drug against a well-established human thyroid cancer cell line, as compared to the free drug
Summary
Identification of effective systemic antineoplastic drugs against anaplastic thyroid carcinomas has important implications. The prognosis of anaplastic thyroid carcinomas is very poor [1,2] Since they are usually unable to concentrate radioiodine, the therapeutical approach is based on combination of aggressive surgery, external beam radiations and chemotherapy. Rarely, this treatment results effective especially for treating metastatic disease [1,2]. A major limit of the chemotherapeutic agents presently used in these tumours, including doxorubicin, paclitaxel and various drug combinations [1,2], is represented by their low therapeutic index. Our data demonstrate that incorporation of gemcitabine in liposomes enhances the cytotoxic effect of the drug against a well-established human thyroid cancer cell line, as compared to the free drug
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