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  • Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells.

    Inflammation-induced radioresistance is mediated by ROS-dependent inactivation of protein phosphatase 1 in non-small cell lung cancer cells.

    부산대 / 김완연, 윤혜숙, 강철희, 윤부현*

  • 출처
    Apoptosis
  • 등재일
    2015 Sep
  • 저널이슈번호
    20(9):1242-52. doi: 10.1007/s10495-015-1141-1.
  • 내용

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    Abstract

    Inflammation plays a pivotal role in modulating the radiation responsiveness of tumors. We determined that an inflammation response prior to irradiation contributes to radiotherapy resistance in non-small cell lung cancer (NSCLC) cells. In the clonogenic survival assay, activation of the inflammation response by lipopolysaccharide (LPS) decreased the degree of radiosensitivity in NCI-H460 cells (relatively radiosensitive cells), but had no effect in A549 cells (relatively radioresistant cells). LPS-induced radioresistance of NCI-H460 cells was also confirmed with a xenograft mouse model. The radioresistant effect observed in NCI-H460 cells was correlated with inhibition of apoptotic cell death due to reduced Caspase 3/7 activity. Moreover, we found that the levels of reactive oxygen species (ROS) were synergistically elevated in NCI-H460 cells by treatment with LPS and radiation. Increased ROS generation negatively affected the activity of protein phosphatase 1 (PP1). Decreased PP1 activity did not lead to Bad dephosphorylation, consequently resulting in the inhibition of irradiation-induced mitochondrial membrane potential loss and apoptosis. We confirmed that pre-treatment with a PP1 activator and LPS sensitized NCI-H460 cells to radiation. Taken together, our findings provided evidence that PP1 activity is critical for radiosensitization in NSCLC cells and PP1 activators can serve as promising radiosensitizers to improve therapeutic efficacy. 

     

    Author information

    Kim W1, Youn H, Kang C, Youn B.

    1Nuclear Science Research Institute, Pusan National University, Busan, 609-735, South Korea.

     

  • 연구소개
    염증반응이 방사선저항성에 미치는 영향을 규명한 논문입니다. 염증반응에 노출된 비소세포폐암 세포에 방사선이 조사되면 ROS가 다량 생성이 되고 이로 인한 protein phosphatase 1(PP1)이 불활성화됩니다. 불활성화된 PP1은 세포사멸유도단백질인 Bad의 탈인산화를 시키지 못해 Bad가 세포사멸기능을 할 수 없게 되어, 결국에는 방사선이 조사되어도 암세포가 살아남게 되는 방사선저항성을 나타내게 됩니다. 본 연구는 환자의 과거병력이 방사선 치료의 효율에 영향을 미칠 수 있음을 뒷받침해주는 의미있는 정보가 될 수 있습니다.
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