Di Desidero Teresa, Antonelli Alessandro, Orlandi Paola, Ferrari Silvia Martina, Fioravanti Anna, Alì Greta, Fontanini Gabriella, Basolo Fulvio, Francia Giulio, Bocci Guido
Dipartimento di Medicina Clinica e Sperimentale, University of Pisa, Pisa, I-56126 Pisa, Italy.
Dipartimento di Patologia Chirurgica, Medica, Molecolare e Dell'Area Critica, University of Pisa, Pisa, I-56126 Pisa, Italy.
Cancer Lett. 2017 Dec 28;411:35-43. doi: 10.1016/j.canlet.2017.09.032. Epub 2017 Sep 28.
The identification of new therapeutic strategies is urgently needed for the management of patients affected by anaplastic thyroid cancer (ATC) due to their short survival and poor prognosis. Aim of the study was to determine the activity of the combination irinotecan/sunitinib on ATC cell growth in vitro and the antitumor effects in vivo. Proliferation assays were performed for 72 h on ATC cell lines exposed to the combination of SN-38, the active metabolite of irinotecan, and sunitinib. The simultaneous combination of sunitinib and SN-38, quantified by the combination index, determined a high synergism on ATC cells, increasing the intracellular concentrations of SN-38. Moreover, the synergistic combination greatly decreases the gene expression and the protein levels of vascular endothelial growth factor, colony stimulating factor 1 and ATP-binding cassette transporter G2 in ATC cells. A significant in vivo antitumor effect was observed in ATC xenografts with the simultaneous combination of irinotecan and sunitinib if compared to monotherapy. The simultaneous combination of irinotecan and sunitinib, in vitro and in vivo demonstrated a significant, synergistic ATC antitumor activity, suggesting a possible and rapid translation of this schedule into the clinics.
由于间变性甲状腺癌（ATC）患者生存期短且预后差，因此迫切需要确定新的治疗策略来管理这类患者。本研究的目的是确定伊立替康/舒尼替尼联合用药对ATC细胞体外生长的活性以及体内抗肿瘤作用。对暴露于伊立替康的活性代谢物SN-38与舒尼替尼联合用药的ATC细胞系进行了72小时的增殖试验。通过联合指数定量的舒尼替尼和SN-38的同时联合用药，对ATC细胞具有高度协同作用，增加了SN-38的细胞内浓度。此外，协同联合用药极大地降低了ATC细胞中血管内皮生长因子、集落刺激因子1和ATP结合盒转运体G2的基因表达和蛋白质水平。与单药治疗相比，伊立替康和舒尼替尼同时联合用药在ATC异种移植模型中观察到显著的体内抗肿瘤作用。伊立替康和舒尼替尼的同时联合用药在体外和体内均显示出显著的协同ATC抗肿瘤活性，表明该方案可能会迅速转化应用于临床。
