OncoTargets and Therapy (Nov 2020)
Lenvatinib Promotes the Antitumor Effect of Doxorubicin in Anaplastic Thyroid Cancer
Abstract
Xi Su,1 Jiaxin Liu,1 Haihong Zhang,1 Qingqing Gu,1 Xinrui Zhou,1 Meiju Ji,2 Demao Yao3 1Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 2Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of China; 3Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, People’s Republic of ChinaCorrespondence: Demao YaoDepartment of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 266, Yanta West Road, Xi’an 710061, People’s Republic of ChinaTel/Fax +86 13991953123Email [email protected] JiCenter for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 266, Yanta West Road, Xi’an 710061, People’s Republic of ChinaTel/Fax +86 29 8532 3259Email [email protected]: Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear.Materials and Methods: The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation was assessed by the MTT assay and colony formation. Flow cytometry was employed to assess ATC cells’ apoptosis and cell cycle arrest in response to combination therapy. Transwell assay was used to test the migration and invasion in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity.Results: Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenograft model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest as compared to lenvatinib or doxorubicin monotherapy.Conclusion: Lenvatinib promotes the antitumor effect of doxorubicin in ATC cell and xenograft model. The lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for anaplastic thyroid cancer.Keywords: anaplastic thyroid cancer, lenvatinib, doxorubicin, combining therapy
