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Azaindole inhibits liver cancer cell proliferation <i>in vitro</i> and <i>in vivo</i> by targeting the expression of kinesin family member C1


Zhen You
Bei Li
Jun Gao
Jiong Lu
Ruihua Xu

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.






Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996