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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 90 - 100 (11page)
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초록· 키워드
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Purpose Non-steroidal anti-inflammatory drugs (NSAIDs) and statins are potential chemopreventiveor chemotherapeutic agents. The mechanism underlying the deregulation of survivin byNSAIDs and statins in human non-small cell lung cancer cells has not been elucidated. Inthis study, we investigated the synergistic interaction of sulindac and simvastatin in lungcancer A549 cells.
Materials and MethodsCell viability was measured by an MTT assay, while the expression of apoptotic markers,AKT, and survivin in response to sulindac and simvastatin was examined by Westernblotting. DNA fragmentation by apoptosis was analyzed by flow cytometry in A549 cells.
Reactive oxygen species (ROS) generation was measured by flow cytometry using H2DCFDAand MitoSOX Red, and the effects of pretreatment with N-acetylcysteine were tested. Theeffects of AKT on survivin expression in sulindac- and simvastatin-treated cells wereassessed. Survivin was knocked down or overexpressed to determine its role in apoptosisinduced by sulindac and simvastatin.
ResultsSulindac and simvastatin synergistically augmented apoptotic activity and intracellular ROSproduction in A549 cells. Inhibition of AKT by siRNA or LY294002 inhibited survivin, whileAKT overexpression markedly increased survivin expression, even in the presence ofsulindac and simvastatin. Moreover, survivin siRNA enhanced sulindac- and simvastatininducedapoptosis. In contrast, survivin upregulation protected against sulindac- andsimvastatin-induced apoptosis.
ConclusionCombined treatment with sulindac and simvastatin augmented their apoptotic potential inlung cancer cells through AKT signaling-dependent downregulation of survivin. These resultsindicate that sulindac and simvastatin may be clinically promising therapies for the preventionof lung cancer.
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참고문헌 (24)
참고문헌 신청
Albayrak A / 2010 / Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats / Pharmacol Rep 62 : 113 ~ 119
Cafforio P / 2005 / Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells / Carcinogenesis 26 : 883 ~ 891
Chan KK / 2003 / The statins as anticancer agents / Clin Cancer Res 9 : 10 ~ 19
Crissman HA / 1993 / Cell cycle-related changes in chromatin structure detected by flow cytometry using multiple DNA fluorochromes / Eur J Histochem 37 : 129 ~ 138
Demierre MF / 2005 / Statins and cancer prevention / Nat Rev Cancer 5 : 930 ~ 942
Cafforio P / 2005 / Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells / Carcinogenesis 26 : 883 ~ 891
Chan KK / 2003 / The statins as anticancer agents / Clin Cancer Res 9 : 10 ~ 19
Crissman HA / 1993 / Cell cycle-related changes in chromatin structure detected by flow cytometry using multiple DNA fluorochromes / Eur J Histochem 37 : 129 ~ 138
Demierre MF / 2005 / Statins and cancer prevention / Nat Rev Cancer 5 : 930 ~ 942
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