Korean J Head Neck Oncol.  2019 Nov;35(2):19-25. 10.21593/kjhno/2019.35.2.19.

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

• Jun S
• Kim SY
• Kim SM
• Park KC
• Kim HJ
• Chang HJ
• Lee YS
• Chang HS
• Park CS

• KMID: 2469230
• DOI: http://doi.org/10.21593/kjhno/2019.35.2.19

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 #SPCHAR_X0026; 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.

Keyword

Anaplastic thyroid cancer; Paclitaxel; Lenvatinib; Radiation

MeSH Terms

Blotting, Western
Caspase 3
Cell Cycle
Cell Death
Cell Line
Cell Survival
Diagnosis
DNA Fragmentation
Flow Cytometry
Heterografts
Humans
In Vitro Techniques*
Paclitaxel*
Protein-Tyrosine Kinases
Survival Rate
Thyroid Carcinoma, Anaplastic*
Thyroid Neoplasms
Tumor Burden
Caspase 3
Paclitaxel
Protein-Tyrosine Kinases