Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma via Akt Signaling Pathway
Low Concentration of Caffeine Inhibits the Progression of the Hepatocellular Carcinoma via Akt Signaling Pathway
复制标题
低浓度咖啡因通过 Akt 信号通路抑制肝细胞癌的进展。
DOI：
10.2174/1871520615666150209110832
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Zheng, Lemin
中科院分区：
文献类型：
--
作者：
Dong, Shuying;Kong, Jian;Zheng, Lemin
越来越多的证据表明，高浓度的咖啡因具有抗癌作用。然而，在低浓度下，特别是在生理适用浓度（< 412 μM）下，咖啡因是否对人肝细胞癌（HCC）细胞具有抗癌作用尚不清楚。本研究使用肝癌细胞系HepG2和Huh7。细胞用不同浓度的咖啡因（0、50、100、200、400或600 μM）孵育。采用MTT法考察其体外增殖能力。通过创面愈合实验和transwell实验测定迁移和侵袭能力。western blot检测分子变化。采用异位裸鼠模型，用咖啡因灌胃小鼠，观察咖啡因对HepG2细胞的体内抗癌作用。结果表明，在生理适宜的浓度下，咖啡因能显著抑制体外培养细胞的增殖、迁移和侵袭。此外，还观察到癌症进展的相关分子变化。在动物实验中，咖啡因灌胃小鼠体内肿瘤负荷也有所减轻。此外，在体内也观察到相关蛋白的表达，这与体外结果一致。综上所述，本研究提示咖啡因可能通过Akt信号通路抑制HCC的进展。这使得咖啡因成为治疗HCC的潜在候选药物，在生理上适用的浓度下长期给予咖啡因将是一种更安全、更有效的治疗方法。
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.