Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs

Berberine Suppressed Tumor Growth through Regulating Fatty Acid Metabolism and Triggering Cell Apoptosis via Targeting FABPs
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小檗碱通过调节脂肪酸代谢和靶向 FABP 触发细胞凋亡来抑制肿瘤生长

DOI:
10.1155/2020/6195050
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发表时间:
2020-04
影响因子:
--
通讯作者:
Yi Ping
Yi Ping
中科院分区:
医学4区
文献类型:
--
作者:
Li Lingli;Peng Ze;Hu Qian;Xu Lijun;Zou Xin;Yu Yan;Huang Dongmei;Yi Ping

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目的进一步探讨小檗碱抗肿瘤作用与脂质代谢的关系。方法采用细胞活力、增殖和凋亡测定法,观察小檗碱对体外培养的人肝癌细胞的生长抑制作用。建立Balb/c裸鼠异位移植瘤模型,观察小檗碱的体内抗肿瘤作用。结果黄连素对人胃癌MGC 803细胞的增殖和存活具有时间和剂量依赖性抑制作用。小檗碱可诱导MGC 803细胞凋亡,且随着小檗碱剂量的增加凋亡率增加。小檗碱诱导MGC 803细胞脂肪酸积累,抑制FABPs和PPARα蛋白表达。FABP抑制剂BMS 309403可重复小檗碱对MGC 803细胞的作用。在异种移植模型中,小檗碱显著减小肿瘤体积和肿瘤重量,并诱导肿瘤组织凋亡。小檗碱可显著提高MGC 803移植瘤模型脂肪酸含量,抑制FABPs和PPARα的表达。结论小檗碱在体内外均能诱导人胃癌细胞凋亡,其机制可能与抑制FABPs蛋白表达和脂肪酸积累有关。
Aim To further investigate the mechanism behind the antitumor properties of berberine regarding lipid metabolism. Methods Cell viability, proliferation, and apoptosis assays were performed to determine the antigrowth effects of berberine in vitro. Ectopic xenograft models in Balb/c nude mice were established to determine the antitumor effects of berberine in vivo. Results Berberine inhibited cell viability and proliferation of MGC803 human gastric cancer cell lines in a time- and dose-dependent manner. Berberine induced apoptosis of MGC803 and increased the apoptotic rate with higher doses. Berberine induced the accumulation of fatty acid of MGC803 and suppressed the protein expression of FABPs and PPARα. The FABP inhibitor BMS309403 recapitulated the effects of berberine on MGC803 cells. In the xenograft model, berberine significantly decreased the tumor volume and tumor weight and induced apoptosis in tumor tissues. Berberine significantly elevated the fatty acid content and inhibited the expression of FABPs and PPARα in the MGC803 xenograft models. Conclusion Berberine exerted anticancer effects on human gastric cancer both in vitro and in vivo by inducing apoptosis, which was due to the reduced protein expression of FABPs and the accumulation of fatty acid.
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