신장암세포주에서 4-(furan-2-yl)-2-(pyridin-2-yl)-5,6-dihydro-1,10-phenanthroline에 의한 항암 효과 및 기전

Other Titles
4-(furan-2-yl)-2-(pyridin-2-yl)-5,6-dihydro-1,10-phenanthroline, a Novel Anti-cancer Agent, Induces Cellular Detachment and Apoptosis in Caki Cells
Authors
윤지혜
Issue Date
2015-12
Awarded Date
2016
Abstract
Anoikis는 부적절한 세포/세포외 기질 부착에 의한 세포자멸사의 한 형태로서 암 치료 분야에서 매력적인 항암 치료 전략이다. FPDHP는 새로 개발된 topoisomerase I 특이 억제제로서 다양한 암 세포주에서 세포자멸사 및 암세포탈락 효과가 있는 것으로 보고되었다. 본 연구에서 A549, HCT116, 및 Caki 세포주에서 FPDHP의 세포자멸사 및 세포탈락 특이 기전을 연구하였다. FPDHP는 Caki, HCT116, 및 A549 세포주에서 세포자멸사와 관련이 없는 세포탈락을 유도하였다. FPDHP는 anoikis 연관 단백질을 조절하였는데, p-FAK, Mcl-1(L), p-Akt, c-FLIP(L), 및 XIAP의 발현을 감소시켰으며, p53의 발현을 증가시켰다. Mcl-1(L), p-Akt 및 c-FLIP(L)이 과발현된 Caki 세포주에서 FPDHP에 의한 세포탈락이 억제되었으나, p53은 FPDHP에 의한 세포탈락에 영향이 없었다. FPDHP는 DEVDase활성화를 동반한 세포자멸사를 유도하였다. Mcl-1(L)의 발현 감소는 FPDHP에 의한 세포자멸사와 관련이 있었다. 이상의 결과는 FPDHP가 폐암, 대장직장암, 및 신장암에서 anoikis 유도 항암제로서 개발 가능성이 있으며, 임상 적용 가능성이 있다고 생각된다.
Anoikis is a type of apoptosis induced by inadequate cell/extracellular matrix (ECM) attachment and an attractive anti-cancer therapeutic strategy in cancer chemotherapeutic field. FPDHP is a newly developed selective topoisomerase I inhibitor and has been reported its apoptotic and cellular detachment activity in various cancer cell lines. In this study, I further evaluated the specific mechanisms of FPDHP on apoptosis and cellular detachment of various human cancer cell lines, including A549 (non small cell lung cancer), HCT116 (colon), and Caki (kidney). FPDHP induced cellular detachment in Caki, HCT116, and A549 cells, irrespective of apoptosis. FPDHP regulated anoikis-related proteins in Caki cells: down-regulations of p-FAK, Mcl-1 (L), p-Akt, c-FLIP (L), and XIAP, and up-regulation of p53. Overexpression of Mcl-1 (L), p-Akt and c-FLIP (L) inhibited FPDHP-induced cellular detachment in Caki cells. However, p53 was not associated with FPDHP-induced cellular detachment in HCT116 cells. FPDHP-induced apoptosis was associated with DEVDase activation. Down-regulation of Mcl-1 (L) was involved in FPDHP-induced apoptosis. Taken together, there findings collectively suggest FPDHP may have potential for developing as an anoikis inducing anti-cancer drug against lung, colorectal, and kidney malignancies, which may deserve further clinical application.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/11322
Appears in Collections:
3. 학위논문 > 1. School of Medicine (의과대학) > 석사
Full Text
http://dcollection.kmu.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000052129
File in this Item
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE