Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma via Akt Signaling Pathway
Accumulating evidences have reported that caffeine has anticancer effects at high blood concentrations.
However, whether caffeine has anticancer effects on human hepatocellular carcinoma (HCC) cells at low
concentration, especially at physiologically applicable concentration (< 412 μM) is still not well understood. In this
study, HCC cell lines HepG2 and Huh7 were used. The cells were incubated with varying concentrations of caffeine (0, 50, 100, 200, 400
or 600 μM). MTT assay was used to investigate the proliferation ability in vitro. Migration and invasion abilities were determined by
wound healing assay and transwell assay. The molecular changes were detected by western blot. An ectopic nude mice model which the
mice were gavaged with caffeine was used to reveal the anticancer effects of caffeine on HepG2 cells in vivo. Results showed that
caffeine could inhibit the proliferation, migration and invasion significantly at physiologically applicable concentration in vitro. Also the
associated molecular changes of cancer progression were observed. In animal experiment, the mice gavaged with caffeine also
performanced reduced tumor burden in vivo. Moreover, the interrelated protein expression was also observed in vivo which was
coincident with the results in vitro. All in all, this observation indicated that caffeine may suppress the progression of HCC through Akt
signaling pathway. This makes caffeine a potential candidate for treating HCC which will be a safer and more effective treatment by
giving for a long time at physiologically applicable concentration.
Keywords: Caffeine, hepatocellular carcinoma, progression, physiologically applicable concentration.
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