PMID- 30567534
DCOM- 20190327
LR  - 20190329
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 18
IP  - 1
DP  - 2018 Dec 19
TI  - Dihomo-gamma-linolenic acid inhibits xenograft tumor growth in mice bearing
      shRNA-transfected HCA-7 cells targeting delta-5-desaturase.
PG  - 1268
LID - 10.1186/s12885-018-5185-9 [doi]
AB  - BACKGROUND: We previously demonstrated that knockdown of delta-5-desaturase via
      siRNA transfection together with dihomo-gamma-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-gamma-linolenic acid peroxidation. Here, we extend our study to
      investigate the effects of delta-5-desaturase-knockdown and the resulting
      intensified dihomo-gamma-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-gamma-linolenic
      acid supplementation, 5-Fluorouracil, and combination of dihomo-gamma-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-gamma-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-gamma-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.
FAU - Xu, Yi
AU  - Xu Y
AD  - Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 
      58105, USA.
FAU - Yang, Xiaoyu
AU  - Yang X
AD  - Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 
      58105, USA.
FAU - Gao, Di
AU  - Gao D
AD  - Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 
      58105, USA.
FAU - Yang, Liu
AU  - Yang L
AD  - Department of Transplantation, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.
FAU - Miskimins, Keith
AU  - Miskimins K
AD  - Cancer Biology Research Center, Sanford Research, Sioux Falls, SD, 57104, USA.
FAU - Qian, Steven Y
AU  - Qian SY
AD  - Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, 
      58105, USA.
LA  - eng
GR  - R15 CA195499/CA/NCI NIH HHS/United States
GR  - R15CA195499/National Cancer Institute
PT  - Journal Article
DEP - 20181219
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (Cadherins)
RN  - 0 (Caprylates)
RN  - 0 (RNA, Small Interfering)
RN  - 764-89-6 (8-hydroxyoctanoic acid)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (delta-5 fatty acid desaturase)
RN  - EC (Cyclooxygenase 2)
RN  - EC (Matrix Metalloproteinase 2)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*administration & dosage
MH  - Animals
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Cadherins/genetics
MH  - Caprylates/metabolism
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/*drug therapy/genetics/pathology
MH  - Cyclooxygenase 2/genetics
MH  - Fatty Acid Desaturases/antagonists & inhibitors/*genetics
MH  - Fluorouracil/administration & dosage
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Matrix Metalloproteinase 2/genetics
MH  - Mice
MH  - Neoplasm Metastasis
MH  - RNA, Small Interfering/genetics
MH  - Xenograft Model Antitumor Assays
PMC - PMC6299961
OT  - COX-2-catalyzed DGLA peroxidation
OT  - Cancer growth and migration
OT  - HDAC inhibitor
OT  - Knockdown of delta-5-desaturase
OT  - Xenograft tumor
EDAT- 2018/12/21 06:00
MHDA- 2019/03/28 06:00
CRDT- 2018/12/21 06:00
PHST- 2018/04/30 00:00 [received]
PHST- 2018/12/05 00:00 [accepted]
PHST- 2018/12/21 06:00 [entrez]
PHST- 2018/12/21 06:00 [pubmed]
PHST- 2019/03/28 06:00 [medline]
AID - 10.1186/s12885-018-5185-9 [doi]
AID - 10.1186/s12885-018-5185-9 [pii]
PST - epublish
SO  - BMC Cancer. 2018 Dec 19;18(1):1268. doi: 10.1186/s12885-018-5185-9.