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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 219 - 229 (11page)
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Purpose 83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis.
Materials and Methods A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis.
Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E2 (PGE2) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450.
Results 83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPAR), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft.
Conclusion The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPAR, and down-regulation of the cancer related genes and molecules.
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참고문헌 (24)
참고문헌 신청
Chan SH / 2013 / Synthesis of 8-hydroxyquinoline derivatives as novel antitumor agents / ACS Med Chem Lett 4 : 170 ~ 174
Deng W / 2004 / Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells : whole-genome evidence
Dimberg J / 2001 / Enhanced expression of cyclooxygenase-2 and nuclear beta-catenin are related to mutations in the APC gene in human colorectal cancer / Anticancer Res 21 :
Fournier T / 2007 / PPARs and the placenta / Placenta 28 : 65 ~ 76
Greenhough A / 2009 / The COX-2/PGE2 pathway : key roles in the hallmarks of cancer and adaptation to the tumour microenvironment / Carcinogenesis 30 : 377 ~ 386
Deng W / 2004 / Distinct profiles of critically short telomeres are a key determinant of different chromosome aberrations in immortalized human cells : whole-genome evidence
Dimberg J / 2001 / Enhanced expression of cyclooxygenase-2 and nuclear beta-catenin are related to mutations in the APC gene in human colorectal cancer / Anticancer Res 21 :
Fournier T / 2007 / PPARs and the placenta / Placenta 28 : 65 ~ 76
Greenhough A / 2009 / The COX-2/PGE2 pathway : key roles in the hallmarks of cancer and adaptation to the tumour microenvironment / Carcinogenesis 30 : 377 ~ 386
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