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Potent antitumor activity of novel taxoids in anaplastic thyroid cancer

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Abstract

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 G2/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 β-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.

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Data availability

The data included in this study are available on request from the corresponding authors.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 82072949 and 81770787 to P.H.), Innovation Talent Promotion Plan in Shaanxi Province (No. 2018TD-006 to P.H.), the Natural Science Foundation Research Project in Shaanxi Province (No. 2019JQ-122 to W.L.), the Open Project Program of Key Laboratory for Tumor Precision Medicine of Shaanxi Province, the first Affiliated Hospital of Xi’an Jiaotong University (No. KLTPM-SX2018-A2 to W.L.), the Natural Science Foundation of Guangdong Province, China (No.2015B020211012 to C.W.) and a grant from the National Institutes of Health, U. S. A. (CA 103314 to I.O.).

Author contributions

P.H. and I.O. conceived and designed the experiments. M.C.W., C.W.W., and C.F. performed the experiments, W.R.G., E.X.L., and W.L. analyzed the data. H.C., B.L., A.T. performed the docking analysis. P.H. and C.W.W. contributed reagents and materials. M.C.W., I.O., and P.H. wrote the paper. All the authors read and approved the final paper.

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Author notes

  1. These authors contributed equally: Meichen Wang, Changwei Wang

Authors and Affiliations

  1. Key Laboratory for Tumor Precision Medicine of Shaanxi Province and Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, China

    Meichen Wang, Chao Feng & Peng Hou

  2. Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

    Meichen Wang & Enxiao Li

  3. Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, NY, 11794-3400, USA

    Changwei Wang & Iwao Ojima

  4. Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 510530, Guangzhou, China

    Changwei Wang & Wanrong Guo

  5. BioBank, The First Affiliated Hospital of Xi’an Jiaotong University, 710061, Xi’an, China

    Huan Chen & Bing Liu

  6. Ultrasound Diagnosis Center, Shaanxi Provincial People’s Hospital, 710068, Xi’an, China

    Wei Liu

  7. Department of Chemistry, Stony Brook University, Stony Brook, NY, 11794-3400, USA

    Adam Taouil & Iwao Ojima

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  1. Meichen Wang
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Correspondence to Iwao Ojima or Peng Hou.

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All animal experiments were conducted and approved by the Laboratory Animal Center of Xi’an Jiaotong University.

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Wang, M., Wang, C., Feng, C. et al. Potent antitumor activity of novel taxoids in anaplastic thyroid cancer. Endocrine 75, 465–477 (2022). https://doi.org/10.1007/s12020-021-02880-1

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