Spalletti-Cernia D, Sorrentino R, Di Gaetano S, Piccoli R, Santoro M, D'Alessio G, Laccetti P, Vecchio G
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy.
Br J Cancer. 2004 Jan 12;90(1):270-7. doi: 10.1038/sj.bjc.6601491.
The lack of selectivity of conventional antitumour drugs against cancer cells is responsible for their high toxicity. The development of new tumour-specific drugs is therefore highly needed. We tested the cytotoxic effects and the nature of cell death induced by a naturally dimeric bovine RNase and a newly engineered dimeric human RNase upon three genetically well-defined normal and malignant thyroid cell systems. RNases effects were compared with those of doxorubicin, a conventional antineoplastic drug. Our results show significant and selective proapoptotic effects exerted on tumour cells by both RNases, the strength of their cytotoxic and apoptotic activity being directly related to the degree of cell malignancy. No toxic effects were observed upon normal cells. Doxorubicin showed, instead, cytotoxic and apoptotic effects also against normal cells. The in vitro results were corroborated by the antitumour action of both dimeric RNases towards a malignant human thyroid tumour grown in nude mice. These results indicate a selective action of dimeric RNases against cancer cells and suggest the potential application of these molecules or their derivatives to the treatment of aggressive subtypes of thyroid cancer.
传统抗肿瘤药物对癌细胞缺乏选择性，这导致了它们的高毒性。因此，迫切需要开发新的肿瘤特异性药物。我们测试了一种天然二聚体牛核糖核酸酶和一种新设计的二聚体人核糖核酸酶对三种基因明确的正常和恶性甲状腺细胞系统的细胞毒性作用以及诱导的细胞死亡性质。将核糖核酸酶的作用与传统抗肿瘤药物阿霉素的作用进行了比较。我们的结果表明，两种核糖核酸酶均对肿瘤细胞产生显著且选择性的促凋亡作用，其细胞毒性和凋亡活性的强度与细胞恶性程度直接相关。未观察到对正常细胞的毒性作用。相反，阿霉素对正常细胞也显示出细胞毒性和凋亡作用。二聚体核糖核酸酶对裸鼠体内生长的恶性人甲状腺肿瘤的抗肿瘤作用证实了体外实验结果。这些结果表明二聚体核糖核酸酶对癌细胞具有选择性作用，并提示这些分子或其衍生物在侵袭性甲状腺癌亚型治疗中的潜在应用。
