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Authors Tang B, Tang F, Wang Z, Qi G, Liang X, Li B, Yuan S, Liu J, Yu S, He S
Received 25 November 2015
Accepted for publication 7 March 2016
Published 30 November 2016 Volume 2016:11 Pages 6401—6420
DOI https://doi.org/10.2147/IJN.S101285
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 4
Editor who approved publication: Dr Lei Yang
Abstract: Primary liver cancer is globally the sixth most frequent cancer, and the
second leading cause of cancer death and its incidence is increasing in many
countries, becoming a serious threat to human health. Many researches focused
on the treatment and prevention of liver cancer. However, due to the underlying
molecular mechanism of liver cancer still not fully understood, the studies and
development of treatments were forced to be delayed. Akt has been suggested to
play an essential role in the progression of inflammation response and
apoptosis. Hence, in this study, Akt-knockout mice and cells of liver cancer
were used as a model to investigate the molecular mechanism of Akt-associated
inflammatory and apoptotic signaling pathway linked with NF-κB and
Bcl-2-associated death promoter (Bad) for the progression of liver cancer.
Carnosic acid (CA), as a phenolic diterpene with anticancer, antibacterial,
antidiabetic, as well as neuroprotective properties, is produced by many
species from Lamiaceae family. Administration of CA nanoparticles was
sufficient to lead to considerable inhibition of liver cancer progression. The
results indicated that, compared to the normal liver cells, the expression of
Akt was significantly higher in liver cancer cell lines. Also, we found that
Akt-knockout cancer cell lines modulated inflammation response and apoptosis
via inhibiting NF-κB activation and inducing apoptotic reaction. Our results
indicated that the downstream signals, including cytokines regulated by NF-κB
and caspase-3-activated apoptosis affected by Bad, were re-modulated for
knockout of Akt. And CA nanoparticles, acting as Akt-knockout, could inhibit
inflammation and accelerate apoptosis in liver cancer by altering NF-κB
activation and activating caspase-3 through Bad pathway. These findings
demonstrated that the nanoparticulate drug CA performed its effective role
owing to its ability to reduce inflammatory action and enhance apoptosis for
the overexpression of NF-κB and Bad via Akt signaling pathway, playing a direct
role in liver cancer progression. Thus, nanoparticle CA might be an important
and potential choice for the clinical treatment in the future.
Keywords: liver cancer, Akt-knockout, carnosic acid nanoparticle, inflammation,
apoptosis