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Dihomo-γ-linolenic acid inhibits xenograft tumor growth in mice bearing shRNA-transfected HCA-7 cells targeting delta-5-desaturase

Xu, Yi ; Yang, Xiaoyu ; Gao, Di ; Yang, Liu ; Miskimins, Keith ; Qian, Steven Y

BMC cancer, 2018-12, Vol.18 (1), p.1268-1268, Article 1268 [Periódico revisado por pares]

England: BioMed Central

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Título:
Dihomo-γ-linolenic acid inhibits xenograft tumor growth in mice bearing shRNA-transfected HCA-7 cells targeting delta-5-desaturase
Autor: Xu, Yi ; Yang, Xiaoyu ; Gao, Di ; Yang, Liu ; Miskimins, Keith ; Qian, Steven Y
Assuntos: 5-Fluorouracil ; 8,11,14-Eicosatrienoic Acid - administration & dosage ; Acid production ; Animals ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Apoptosis ; Breast cancer ; Cadherins - genetics ; Cancer growth and migration ; Cancer therapies ; Caprylates - metabolism ; Cell adhesion & migration ; Cell growth ; Cell Line, Tumor ; Cell migration ; Colon cancer ; Colonic Neoplasms - drug therapy ; Colonic Neoplasms - genetics ; Colonic Neoplasms - pathology ; Colorectal cancer ; COX-2-catalyzed DGLA peroxidation ; Cyclooxygenase 2 - genetics ; Cyclooxygenase-2 ; Desaturase ; Diet ; E-cadherin ; Enzymes ; Fatty Acid Desaturases - antagonists & inhibitors ; Fatty Acid Desaturases - genetics ; Fatty acids ; Fluorouracil - administration & dosage ; Gelatinase A ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Knockdown Techniques ; HDAC inhibitor ; Humans ; Knockdown of delta-5-desaturase ; Linolenic acid ; Lipids ; Liver cancer ; Lung cancer ; Matrix Metalloproteinase 2 - genetics ; Metastases ; Metastasis ; Mice ; Nanotechnology ; Neoplasm Metastasis ; p53 Protein ; Peroxidation ; RNA, Small Interfering - genetics ; siRNA ; Supplements ; Transfection ; Tumor cells ; Tumors ; Xenograft Model Antitumor Assays ; Xenograft tumor ; Xenografts
É parte de: BMC cancer, 2018-12, Vol.18 (1), p.1268-1268, Article 1268
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: We previously demonstrated that knockdown of delta-5-desaturase via siRNA transfection together with dihomo-γ-linolenic acid supplementation inhibited colon cancer cell growth and migration, by promoting the production of the anti-cancer byproduct 8-hydroxyoctanoic acid from Cyclooxygenase-2-catalyzed dihomo-γ-linolenic acid peroxidation. Here, we extend our study to investigate the effects of delta-5-desaturase-knockdown and the resulting intensified dihomo-γ-linolenic acid peroxidation in xenograft tumor mice model. Four-week old nude mice bearing the human colon cancer cell HCA-7/C29 vs. its delta-5-desaturase knockdown analog (via shRNA transfection) were subject to 4-week treatments of: vehicle control, dihomo-γ-linolenic acid supplementation, 5-Fluorouracil, and combination of dihomo-γ-linolenic acid and 5-Fluorouracil. Tumor growth was monitored during the treatment. At the endpoint, the mice were euthanized and the tumor tissues were collected for further mechanism analysis. Delta-5-desaturase knockdown (shRNA) together with dihomo-γ-linolenic acid supplementation increased 8-hydroxyoctanoic acid production to a threshold level in xenograft tumors, which consequently induced p53-dependent apoptosis and reduced tumors significantly. The promoted 8-hydroxyoctanoic acid formation was also found to suppress the tumors' metastatic potential via regulating MMP-2 and E-cadherin expressions. In addition, our in vivo data showed that delta-5-desaturase knockdown along with dihomo-γ-linolenic acid supplementation resulted in anti-tumor effects comparable to those of 5-Fluorouracil. We have demonstrated that our paradigm-shifting strategy of knocking down delta-5-desaturase and taking advantage of overexpressed Cyclooxygenase-2 in tumor cells can be used for colon cancer suppression. Our research outcome will lead us to develop a better and safer anti-cancer therapy for patients.
Editor: England: BioMed Central
Idioma: Inglês

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Dihomo-γ-linolenic acid inhibits xenograft tumor growth in mice bearing shRNA-transfected HCA-7 cells targeting delta-5-desaturase

Xu, Yi ; Yang, Xiaoyu ; Gao, Di ; Yang, Liu ; Miskimins, Keith ; Qian, Steven Y

England: BioMed Central

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