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Paclitaxel, Lenvatinib 및 방사선 병용 요법의 역형성 갑상선암에서의 항암 작용

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

  • 전시열 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 김수영 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 김석모 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 박기청 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 김희준 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 장호진 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 이용상 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 장항석 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터) ;
  • 박정수 (연세대학교 의과대학 강남세브란스병원 외과학교실 갑상선암센터)
  • Jun, Shiyeol (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Kim, Soo Young (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Kim, Seok-Mo (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Park, Ki Cheong (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Kim, Hee Jun (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Chang, Ho Jin (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Lee, Yong Sang (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Chang, Hang-Seok (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine) ;
  • Park, Cheong Soo (Thyroid Cancer Center, Gangnam Severance Hospital, Department of Surgery, Yonsei University College of Medicine)
  • 투고 : 2019.10.31
  • 심사 : 2019.11.15
  • 발행 : 2019.11.30

초록

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

참고문헌

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