Journal of Digestive Cancer Research

Korean Society of Gastrointestinal Cancer Research (대한소화기암연구학회)
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Model for Cancer Cachexia using C26 Adenocarcinoma-Induced Wasting Syndrome for Newer Therapeutic Approach

새로운 치료 방법 접근을 위한 C26 선암세포 기반의 Cancer Cachexia 동물모델 수립

  • Eun A Kang (CHA Cancer prevention Research Center, CHA University Bio Complex) ;
  • Jong Min Park (CHA Cancer prevention Research Center, CHA University Bio Complex) ;
  • Young Min Han (CHA Cancer prevention Research Center, CHA University Bio Complex) ;
  • Sung Pyo Hong (Digestive Disease Center, CHA University Bundang Medical Center) ;
  • Joo Young Cho (Digestive Disease Center, CHA University Bundang Medical Center) ;
  • In Kyung Yoo (Digestive Disease Center, CHA University Bundang Medical Center) ;
  • Ji Young Oh (CJ Food Research Institute) ;
  • Ki Baik Hahm (CHA Cancer prevention Research Center, CHA University Bio Complex)
  • 강은아 (차의과학대학교 CHA Bio Complex) ;
  • 박종민 (차의과학대학교 CHA Bio Complex) ;
  • 한영민 (차의과학대학교 CHA Bio Complex) ;
  • 홍성표 (분당차병원 소화기센터) ;
  • 조주영 (분당차병원 소화기센터) ;
  • 유인경 (분당차병원 소화기센터) ;
  • 오지영 (CJ Food 연구소) ;
  • 함기백 (차의과학대학교 CHA Bio Complex)
  • Received : 2017.09.19
  • Accepted : 2017.12.14
  • Published : 2017.12.31
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Abstract

Background: Cachexia is a multi-factorial syndrome presenting with chronic illness, decreases in body weight, and loss of adipose tissue and skeletal muscle, mostly in patients with advanced cancer and chronic wasting disease. Even after years of intensive researches, there remains no convincing therapy to prevent cancer cachexia. Methods: In this in vivo study, we have established C26 adenocarcinoma-induced cancer cachexia model in mice to explore the underlying core changes in cytokine, signal transduction, and muscle wasting. The ultimate aim of establishing animal model is to find optimal therapeutics to mitigate cancer cachexia. Results: We have administered C26 adenocarcinoma cells onto BALB/c mice and observed 4 weeks to assess the progression of cancer cachexia. Significant loss of weight accompanied with loss of appetite was noted. As C26 adenocarcinoma xenograft progressed, mortality was started from 3 weeks, accompanied with significant sarcopenia and decreased mice movement. Surges in TNF-α and IL-6 were noted with the commencement of cancer cachexia. Conclusion: Using C26 adenocarcinoma cancer cachexia model, we can screen the optimal therapeutics to mitigate cancer cachexia, in which agents to modulate IL-6, TNF-α, and NF-κB were essential.

Cancer cachexia는 지방조직과 근육계 조직의 손실에 따른 체중의 현격한 감소를 특징으로 하고 있어 궁극적으로는 암 치료제에 대한 반응을 낮출 뿐만 아니라, 삶의 양은 물론 질도 낮추게 되는 시급히 해결되어야 하는 미충족 의료수요중의 하나이다. 아직까지 임상에서는 수많은 노략에도 불구하고 일부 완화시킬 수 있는 약제가 있기는 하나, 전반적으로 해결이 가능한 약제나 치료 방법이 아직은 없는 실정이다. 그러므로 이를 해결할 수 있는 방법으로 동물모델이 필요한 질환이라 하겠다. 이러한 배경하에 연구자 등은 우선 동물모델을 수립하고 이를 기반으로 적절한 치료제를 개발하기 목적으로 본 연구에서는 C26 대장 선암 세포를 이용한 Cancer cachexia 동물모델을 수립하여 이 모델에서의 변화를 소개함으로써 향후 더 진보된 치료제 개발이나 병태생리를 연구하는데 도움을 주고자 본 연구를 시행하여 다음과 같은 결과를 얻을 수 있었다. C26 adenocarcinoma를 대퇴부 주입 후 시간 경과에 따라 몸무게의 변화가 현저하여 2주 이후에 유의한 몸무게의 감소, 식욕부진, 활동감소가 관찰되었고, 이때의 혈청 Cytokine 및 이를 조절하는 여러가지 전사인자의 변화가 선행되었고, 현저한 근육계의 근감소가 관찰되었으며, 실험동물은 3주에 40%가 사망하는 변화를 보였다. 연구자 등은 본 동물모델은 향후 새로운 치료약제 개발이나 Cancer cachexia 병태생리 연구에 매우 도움이 되는 수립하기 간편하며, 기저 분자생물학적 변화를 관찰할 수 있는 우수한 Cancer cachexia 모델이라 결론지을 수 있었다.

Keywords

Acknowledgement

이 성과는 2017년도 정부(미래창조과학부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구(No. NRF-2017R1C1B2009057)와 농림축산식품부의 재원으로 농림수산식품기술기획평가원의 고부가가치식품기술개발사업의 지원을 받아서 연구되었음(No. 116015-03-1-CG000).

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