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Anti-cancer Activity of Paclitaxel, Lenvatinib and Radiation Combination Therapy on Anaplastic Thyroid Cancer in Vitro and in Vivo

대한두경부종양학회지 2019년 35권 2호 p.19 ~ 25
전시열 ( Jun Shi-Yeol ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery

김수영 ( Kim Soo-Young ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
김석모 ( Kim Seok-Mo ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
박기청 ( Park Ki-Cheong ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
김희준 ( Kim Hee-Jun ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
장호진 ( Chang Ho-Jin ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
이용상 ( Lee Yong-Sang ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
장항석 ( Chang Hang-Seok ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery
박정수 ( Park Cheong-Soo ) - Yonsei University College of Medicine Gangnam Severance Hospital Department of Surgery

Abstract


Background/Objectives: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the deadliest forms of thyroid cancer. The fatality rate for ATC is high, and the survival rate at one year after diagnosis is <20%.
The present study aimed to investigate the anti-tumor activities of paclitaxel, radiation, and tyrosine kinase inhibitor (TKI) combined therapy in anaplastic thyroid cancer cells both in vitro and in vivo and explore its effects on apoptotic cell death pathways.

Materials & Methods: ATC cell line was exposed to TKI, lenvatinib in the presence or absence of paclitaxel with radiation, and cell viability was determined by MTT assay. Effects of the combined treatment on cell cycle and intracellular signaling pathways were assessed by flow cytometry and western blot analysis. The ATC cell line xenograft model was used to examine the anti-tumor activity in vivo.

Results: Our data revealed that the combined administration of paclitaxel, TKI, and radiation decreased cell viability in ATC cells, and also significantly increased apoptotic cell death in these cells, as demonstrated by the cleavage of caspase-3 and DNA fragmentation. This combination therapy reduced anti-apoptotic factor levels in ATC cells, while significantly decreasing tumor volume and increasing survival in ATC xenografts.

Conclusion: These results indicate that administering the combination of paclitaxel, TKI, and radiation therapy may exert significant anticancer effects in preclinical models, potentially suggesting a new clinical approach for treating patients with ATC.

키워드

Anaplastic thyroid cancer; Paclitaxel; Lenvatinib; Radiation
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