Gene/Protein
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Target Concepts:
Gene/Protein
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Query: UMLS:C1864663 (
HCC
)
2,985
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Simultaneous silencing of multiple up-regulated genes is an attractive and viable strategy to treat many incurable diseases including cancer. Herein we used dual gene targeted siRNA (DGT siRNA) conjugate composed of
NET-1
and VEGF siRNA sequences in the same backbone could inhibit growth and angiogenesis
HCC
. DGT siRNA showed a further down regulation on VEGF mRNA and protein levels compared with
NET-1
siRNA or VEGF siRNA, but not on
NET-1
expression. It also exhibited greater suppression on proliferation and trigger of apoptosis in HepG2 cells than
NET-1
siRNA or VEGF siRNA; this could be explained by the significant down regulation of cyclin D1 and Bcl-2. A lower level of ANG2 mRNA and protein was detected in HUVEC cultured with supernatant of HepG2 cells treated with DGT siRNA than that of VEGF siRNA or
NET-1
siRNA, resulting in much more inhibited angiogenesis of HUVEC. Tumor growth was inhibited and microvessel density dropped in the xenograft tumor models compared to the untreated controls.
NET-1
and VEGF silencing play a key role in inhibiting hepatocellular cell proliferation, promoting apoptosis, and reducing angiogenesis. Simultaneous silencing of
NET-1
and VEGF using DGT siRNA construct may provide an advantageous alternative in development of therapeutics for Hepatocellular carcinoma.
...
PMID:Inhibition of hepatocellular carcinoma growth and angiogenesis by dual silencing of NET-1 and VEGF. 2363 6
The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting
NET-1
or combined with sorafenib on
HCC
in vitro and in vivo and the possible underlying mechanisms. The expressions of
NET-1
mRNA and protein were detected by RT-QPCR and western blot. The ability of proliferation was determined by CCK-8 assay. Apoptosis was examined by flow cytometry (FCM). Abilities of migration and invasion were measured by scratch-wound assay and transwell assay. MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of
HCC
and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined.
NET-1
mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA. The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P < 0.05). The mRNA levels of caspase-3, caspase-8, and caspase-9 of tumor tissues were reduced in different treatment groups compared with untreated group, particularly in combination group. (P < 0.05). The combination NET-1shRNA with sorafenib dramatically enhanced the effects of sorafenib antitumor ,which may involve in blocking ras signaling pathway and stimulating apoptotic pathways simultaneously.
...
PMID:Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro and In Vivo. 2430 93
