Potent antitumor activity of novel taxoids in anaplastic thyroid cancer
Potent antitumor activity of novel taxoids in anaplastic thyroid cancer
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DOI：
10.1007/s12020-021-02880-1
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发表时间：
2021-09-30
期刊：
影响因子：
3.7
通讯作者：
Hou, Peng
中科院分区：
文献类型：
--
作者：
Wang, Meichen;Wang, Changwei;Hou, Peng
目的甲状腺未分化癌（Anaplastic thyroid cancer，ATC）是甲状腺癌中最具侵袭性的一种，在没有有效治疗方案的情况下可迅速致死。已有临床试验表明，以紫杉醇为基础的化疗方案治疗ATC可获得较高的缓解率和较低的不良反应发生率。本研究的目的是评估新型紫杉烷类化合物在ATC细胞中的潜在治疗活性。方法通过一系列体内外实验，评价5种新型3 '-二氟乙烯基紫杉醇类化合物（DFV-taxoids）对甲状腺未分化癌细胞的抗肿瘤活性。此外，我们还通过分子对接和微管蛋白聚合实验，探讨了紫杉烷类化合物和紫杉醇之间差异的潜在机制。结果与紫杉醇相比，新型紫杉醇类化合物对ATC细胞增殖、集落形成和裸鼠成瘤能力的抑制作用更强，并能诱导ATC细胞发生G2/M期阻滞和凋亡。使用微管蛋白聚合测定和分子对接分析，我们发现这些DFV-紫杉烷比紫杉醇更快地促进β-微管蛋白的聚合。结论新紫杉烷类化合物对ATC细胞的抗肿瘤活性强于紫杉醇，为ATC患者的治疗提供了新的思路。
Purpose Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancers and it is rapidly fatal without any effective therapeutic regimens. There are some clinical trials showing that paclitaxel-based chemotherapy for ATC can achieve a relatively high response rate and low incidence of adverse reaction. The aim of this study was to evaluate potential therapeutic activity of novel taxoids in ATC cells. Methods We evaluated antitumor activity of five novel 3 '-difluorovinyltaxoids (DFV-taxoids) in anaplastic thyroid cancer cells by a series of in vitro and in vivo experiments. Besides, we also explored the potential mechanism underlying the difference among the taxoids and paclitaxel by molecular docking and tubulin polymerization assays. Results Our data showed that these novel DFV-taxoids were more effective than paclitaxel in ATC cell lines and xenografts, as reflected by the inhibition of cell proliferation, colony formation and tumorigenic potential in nude mice, and the induction of G(2)/M phase arrest and cell apoptosis. Using tubulin polymerization assays and molecular docking analysis, we found that these DFV-taxoids promoted more rapid polymerization of beta-tubulin than paclitaxel. Conclusions Our data demonstrate that these novel taxoids exhibit stronger antitumor activity in ATC cells than paclitaxel, thereby providing a promising therapeutic strategy for the patients with ATC.