Abstract

 
 
 
 Purpose: To investigate the effect of azaindole on proliferation of liver cancer cells, as well as the underlying mechanism.
 Methods: Colony forming and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were used to determine the effect of azaindole on cell proliferation. A tumor model was established through subcutaneous administration of HEPG2 cells to rats. Thereafter, in vivo tumor development was measured using Vernier caliper.
 Results: The proliferation potential of HEPG2 and SNU-398 cells was markedly and dose-dependently suppressed by treatment with azaindole at doses of 2, 4, 8, 16 and 20 μM (p < 0.05). The expression levels of Ki67 and PCNA levels were significantly down-regulated in HEPG2 and SNU-398 cells on treatment with 20 μM azaindole. Moreover, azaindole significantly suppressed mRNA and protein expressions of KIFC1 in HEPG2 and SNU-398 cells (p < 0.05). Tumor volume in azaindole-treated rats on day 21 was greatly reduced, while KIFC1 expression in azaindole-treated rat tumor tissue was significantly down-regulated, when compared to the model group (p < 0.05).
 Conclusion: Azaindole targets proliferation of liver cancer cells in vitro and inhibits tumor growth in vivo through a mechanism involving down-regulation of KIFCI expression. Thus, azaindole is a potential therapeutic candidate for liver cancer.
 
 
 
Highlights
Liver cancer is a malignant tumor which is ranked the third highest cause of mortality throughout the world [1]
At doses of 2, 4, 8, 16 and 20 μM, azaindole decreased the proliferative potential of HEPG2 cells to 90, 74, 59, 42 and 28 %, respectively
At a dose of 20 μM, azaindole markedly inhibited the growth of colonies formed by HEPG2 and SNU398 cells, when compared to the untreated cells (p < 0.05)
Summary
Liver cancer is a malignant tumor which is ranked the third highest cause of mortality throughout the world [1]. The rate of cell proliferation and chances of survival are largely influenced by KIFC1 expression [9]. The effect of azaindole on liver cancer cell proliferation and tumor growth was investigated. 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) was added to each plate, and cell incubation was continued for additional 4 h This was followed by replacement of the medium in each well with DMSO (150 μL) so as to solubilize the resultant formazan crystals. Thereafter, the membranes were washed with PBS, followed by 1 h incubation with goat anti-rabbit secondary antibody at room temperature. The sequences of the primers used were: 30 min, followed by incubation for 2 h with anti-KIFC1 antibodies at 37 ̊C. Thereafter, the rats were sacrificed using cervical dislocation under sodium sorbitol anesthesia
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