Pharmacological effects of vinorelbine in combination with lenvatinib in anaplastic thyroid cancer.
Pharmacological effects of vinorelbine in combination with lenvatinib in anaplastic thyroid cancer.
复制标题
DOI：
10.1016/j.phrs.2020.104920
复制
发表时间：
2020-08
影响因子：
9.3
通讯作者：
Bocci G
中科院分区：
文献类型：
--
作者：
Di Desidero T;Orlandi P;Gentile D;Banchi M;Alì G;Kusmic C;Armanetti P;Cayme GJ;Menichetti L;Fontanini G;Francia G;Bocci G
甲状腺未分化癌是一种罕见的肿瘤，预后差。对暴露于长春瑞滨、乐伐替尼以及伴随组合的ATC细胞系（8305 C、8505 C）进行增殖和凋亡试验。采用真实的时间PCR检测ABCB 1、ABCG 2和CSF-1 mRNA的表达。作为人磷酸激酶阵列分析的一部分，研究pospho Akt的相对水平，并通过ELISA测量CSF-1和VEGFR-2蛋白水平。通过联合反相液相色谱-串联质谱法测定ATC细胞中乐伐替尼的细胞内浓度。用长春瑞滨、乐伐替尼或长春瑞滨+乐伐替尼治疗裸鼠ATC皮下异种移植瘤模型。在用长春瑞滨、乐伐替尼处理后，在ATC细胞系中观察到显著的抗增殖作用。长春瑞滨和乐伐替尼的联合治疗显示出对受影响细胞的所有部分具有协同作用。在接受乐伐替尼+长春瑞滨联合给药的两种ATC细胞系中均报告了ABCB 1表达降低，以及细胞内乐伐替尼浓度升高。联合用药导致Akt、GSK 3 α/β、PRAS 40和Src磷酸化以及CSF-1 mRNA和蛋白水平降低。在皮下肿瘤模型中，该组合在治疗期间减小了肿瘤体积。我们的研究结果确立了长春瑞滨和乐伐替尼联合用药的协同ATC抗肿瘤活性。
Anaplastic thyroid cancer (ATC) is a rare neoplasia with a poor prognosis. Proliferation and apoptosis assays were performed on ATC cell lines (8305C, 8505C) exposed to vinorelbine, lenvatinib, as well as to concomitant combinations. ABCB1, ABCG2 and CSF-1 mRNA expression was evaluated by real time PCR. The relative levels of pospho Akt were investigated as part of a human phospho-kinase array analysis, and CSF-1 and VEGFR-2 protein levels were measured by ELISA. The intracellular concentration of lenvatinib in ATC cells was measured by combined reversed-phase liquid chromatography-tandem mass spectrometry. An ATC subcutaneous xenograft tumor model in nude mice was treated with vinorelbine, lenvatinib, or vinorelbine plus lenvatinib. After treatment with vinorelbine, lenvatinib, a significant antiproliferative effect in ATC cell lines was observed. The concomitant treatment of vinorelbine and lenvatinib revealed synergism for all the fractions of affected cells. A decrease in ABCB1 expression was reported in both ATC cell lines treated with the lenvatinib plus vinorelbine combination, as was an increase in the intracellular concentration of lenvatinib. The combination caused a decrease in Akt, GSK3α/β, PRAS40 and Src phosphorylation, and in both CSF-1 mRNA and protein levels. In the subcutaneous tumor model, the combination reduced the tumor volume during the treatment period. Our results establish the synergistic ATC antitumor activity of a vinorelbine and lenvatinib combination.
登录
查看更多内容
影响因子：
4.8
作者：
Canu, Bastianina;Fioravanti, Anna;Bocci, Guido
通讯作者：
Bocci, Guido
影响因子：
5.8
作者：
Di Desidero, Teresa;Fioravanti, Anna;Bocci, Guido
通讯作者：
Bocci, Guido
影响因子：
4.7
作者：
Di Desidero, Teresa;Orlandi, Paola;Bocci, Guido
通讯作者：
Bocci, Guido
DOI：
10.1158/1078-0432.ccr-11-3359
发表时间：
2012-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chan CM;Jing X;Pike LA;Zhou Q;Lim DJ;Sams SB;Lund GS;Sharma V;Haugen BR;Schweppe RE
通讯作者：
Schweppe RE
影响因子：
4.2
作者：
Ferrari, Silvia Martina;Bocci, Guido;Fallahi, Poupak
通讯作者：
Fallahi, Poupak