Re-sensitization of radiation resistant colorectal cancer cells to radiation through inhibition of AMPK pathway.
Radiotherapy (RT) is commonly used to treat multi-tumors to attenuate the risk of recurrence. Despite impressive initial clinical responses, a large proportion of patients experience resistance to RT. Therefore, identification of functionally relevant biomarkers would be beneficial for radioresistant patients. Adenosine monophosphate-activated kinase (AMPK) is recognized as a mediator of tumor suppressor gene function. In the present study, radio-sensitive and -resistant colon cancer patient samples were compared and the AMPK pathway was observed to be highly activated in radioresistant patients. In addition, the protein and mRNA levels of AMPK were upregulated in radioresistant colon cancer cells in comparison to radiosensitive colon cancer cells. The present study provides evidence that activation of AMPK by metformin contributes to radioresistance. Inhibition of AMPK by either small interfering RNA or Compound C, which is a specific inhibitor of AMPK, re-sensitized radiation resistant cells. The data presented indicates a synergistic effect on radiation resistant cancer cells by the combination of Compound C and radiation. In summary, the present study proposes that inhibition of the AMPK pathway is a potential strategy for reversing radiation resistance and may contribute to the development of therapeutic anticancer drugs.
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Hongyong
H
Jin
Department of Anesthesia, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Sujie
S
Gao
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Huiling
H
Guo
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Shengnan
S
Ren
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Fujian
F
Ji
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Zhuo
Z
Liu
Department of General Surgery, China Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Xuebo
X
Chen
AMPK; colorectal cancer; compound C; metformin; radioresistance