Abstract
Background: To investigate the effects of Artesunate (ART) on cell
proliferation inhibition, apoptosis as well as gene expression of
leukemic monocytic lymphoma cell line U937, and discuss the underlying
mechanism. Methods: U937 cells were divided into groups treated by ART
at different concentrations. Inhibiting effects of ART were determined
by CCK-8 assay. Illumina Hiseq platform combined with q-PCR technology
was applied to select the specific differentially expressed gene (DEG)
between ART treated group and control group; Cell apoptosis was
investigated by flow cytometry, and the expressions of apoptosis-related
proteins were detected by western blot with CCDC102A being interfered.
Results: ART possessed inhibitory effect on U937 cells proliferation in
a concentration-dependent manner. The cell viability was no longer
decreasing after the concentration of ART increased to 50 mg/L. CCDC102A
gene was selected as the target gene through DEGs analysis to be
interfered, in order to study the effects on U937. After interfered
CCDC102A, the proliferation of U937 was inhibited, while the apoptosis
was enhanced, the expressions of pro-apoptotic proteins such as Bax,
Active-Caspase3 as well as p53 were increased, and the expression of
anti-apoptotic protein Bcl2 was suppressed. Furthermore, the expressions
of proteins in PI3K/Akt/mTOR signaling pathway such as AKT, p-AKT and
mTOR were inhibited. Conclusion: ART can inhibit growth of U937 cell and
induce apoptosis. CCDC102A gene may be involved in the anti-cancer
effects of ART through induction apoptosis of U937 cells via
up-regulation of Bax/Bcl2 levels and inhibition of Akt-mTOR signaling
pathways.