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http://purl.uniprot.org/citations/30567534http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30567534http://www.w3.org/2000/01/rdf-schema#comment"

Background

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.

Methods

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.

Results

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.

Conclusions

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."xsd:string
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http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Gao D."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Yang X."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Yang L."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Xu Y."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Qian S.Y."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/author"Miskimins K."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/name"BMC Cancer"xsd:string
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http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/title"Dihomo-gamma-linolenic acid inhibits xenograft tumor growth in mice bearing shRNA-transfected HCA-7 cells targeting delta-5-desaturase."xsd:string
http://purl.uniprot.org/citations/30567534http://purl.uniprot.org/core/volume"18"xsd:string
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