생명과학회지 (Journal of Life Science)

  • 제19권12호
  • /
  • Pages.1705-1711
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  • 2009
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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시스플라틴 내성세포주에서 열충격에 의한 세포사멸에 관한 연구

Heat Shock Induces Necrosis in Cisplatin-resistant Gastric Cancer Cells through Suppressing JNK1/2 Activation and HSP27 Induction

  • 임성철 (조선대학교 내성세포센터) ;
  • 최철희 (조선대학교 내성세포센터) ;
  • 한송이 (조선대학교 내성세포센터)
  • Lim, Sung-Chul (Research Center for Resistant Cells, Chosun University) ;
  • Choi, Cheol-Hee (Research Center for Resistant Cells, Chosun University) ;
  • Han, Song-Iy (Research Center for Resistant Cells, Chosun University)
  • 발행 : 2009.12.30
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초록

항암제 내성을 획득한 암세포는 많은 경우 다양한 세포 독성 물질에 대해 교차 내성을 나타낸다. 그러나 온열 치료가 내성 획득 종양에 적용 될 때의 종양 세포의 사멸 효과는 알려져 있지 않다. 본 연구는 시스플라틴에 내성을 갖는 위암 세포 주, SNU601/Cis2이 열충격에 반응하는 민감도와 세포 사멸 방식을 조사함으로써 약물 내성 종양의 온열 치료 효과를 예측하고자 하였다. 정상 위암 세포 주 SNU601/WT은 열충격에 매우 민감하게 반응하며 apoptosis로 사멸하지만, 내성 위암 세포 주 SNU601/Cis2는 미열충격에 내성을 나타내었으며 고열충격에 노출되자 necrosis로 사멸하였다. 또한 SNU601/Cis2에서 necrosis의 발생은 열충격에 의한 JNK1/2의 활성화와 HSP27의 발현저하 현상과 관련되어 있었다. Necrosis의 유도는 세포막 파괴에 의해 세포 내부 물질의 방출로 인한 주변 조직의 염증반응을 수반하는데, 이러한 염증 반응은 암의 성장을 촉진하고 암의 성상을 심화시키는 것으로 보고되고 있다. 이러한 관점에서, 온열 치료가 약물 치료와 병행 될 경우에는 교차 내성과 necrosis로 인한 역효과를 방지하기 위하여, 그 적용이 주의 깊게 이루어져야 할 것으로 판단된다.

Carcinoma cells that had acquired resistance to a chemotherapeutic drug often show cross-resistance to various other cytotoxic drugs. In the present study, we explored the effect of heat shock in cisplatin-resistant gastric cancer cells SNU601/Cis2 to figure out the efficacy of hyperthermia in drug-resistant carcinoma. While SNU601/WT cells showed a high-sensitivity response to heat shock by dying through apoptosis, SNU601/Cis2 cells were considerably resistant to mild heat shock, but died by necrosis upon treatment with harsh heat shock. The occurrence of necrosis in SNU601/Cis2 cells was linked to the suppression of both JNK1/2 activation and HSP27 induction in response to heat shock. Since necrosis is closely associated with tumor malignancy and poor prognosis through inflammatory responses, our result suggests that hyperthermic treatment should be carefully applied when it is combined with chemotherapy.

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