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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 109 - 114 (6page)
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The COX-2/PGE2 pathway has been implicated in the occurrenceand progression of cancer. The underlying mechanismsfacilitating the production of COX-2 and its mediator,PGE2, in cancer survival remain unknown. Herein, weinvestigated PGE2-induced COX-2 expression and signaling inHL-60 cells following menadione treatment. Treatment withPGE2 activated anti-apoptotic proteins such as Bcl-2 and Bcl-xLwhile reducing pro-apoptotic proteins, thereby enhancing cellsurvival. PGE2 not only induced COX-2 expression, but alsoprevented casapse-3, PARP, and lamin B cleavage. Silencingand inhibition of COX-2 with siRNA transfection or treatmentwith indomethacin led to a pronounced reduction of theextracellular levels of PGE2, and restored the menadione-induced cell death. In addition, pretreatment of cells withthe MEK inhibitor PD98059 and the PKA inhibitor H89abrogated the PGE2-induced expression of COX-2, suggestinginvolvement of the MAPK and PKA pathways. These resultsdemonstrate that PGE2 signaling acts in an autocrine manner,and specific inhibition of PGE2 will provide a novel approachfor the treatment of leukemia.
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참고문헌 (21)
참고문헌 신청
Basnakian AG / 1994 / A rapid and sensitive assay for the detection of DNA fragmentation during early phases of apoptosis / Nucleic Acids Res 22 : 2714 ~ 2715
Blobaum AL / 2013 / The 2'-trifluoromethyl analogue of indomethacin is a potent and selective COX-2 inhibitor / ACS Med Chem Lett 9 : 486 ~ 490
Cao Y / 2002 / Many actions of cyclooxygenase-2 in cellular dynamics and in cancer / J Cell Physiol 190 : 279 ~ 286
Fadeel B / 1999 / Cleavage of Bcl-2 is an early event in chemotherapy-induced apoptosis of human myeloid leukemia cells / Leukemia 13 : 719 ~ 728
Harris RE / 2009 / Cyclooxygenase-2(COX-2)blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung / Inflammopharmacology 17 : 55 ~ 67
Blobaum AL / 2013 / The 2'-trifluoromethyl analogue of indomethacin is a potent and selective COX-2 inhibitor / ACS Med Chem Lett 9 : 486 ~ 490
Cao Y / 2002 / Many actions of cyclooxygenase-2 in cellular dynamics and in cancer / J Cell Physiol 190 : 279 ~ 286
Fadeel B / 1999 / Cleavage of Bcl-2 is an early event in chemotherapy-induced apoptosis of human myeloid leukemia cells / Leukemia 13 : 719 ~ 728
Harris RE / 2009 / Cyclooxygenase-2(COX-2)blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung / Inflammopharmacology 17 : 55 ~ 67
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