Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway.

Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway.
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小檗碱通过腺苷单磷酸激活蛋白激酶途径抑制糖酵解,从而抑制胰腺上皮内瘤变。

DOI:
10.1016/j.ejphar.2021.174680
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发表时间:
2021-12
影响因子:
5
通讯作者:
Yue Pan
Yue Pan
中科院分区:
医学2区
文献类型:
--
作者:
Liu Mengmeng;Yang Yongjie;Kang Wenli;Liu Yingjie;Tao Xufeng;Li Xiaona;Yue Pan

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大多数胰腺癌发生于慢性胰腺炎(CP)患者。小檗碱是一种天然产物,对各种类型的癌症都有抗肿瘤作用,被用于中药中。在本研究中,我们证明了小檗碱在兔蛋白vivoCP模型和兔蛋白体外腺泡-导管化生模型中抑制胰腺上皮内瘤变(PanIN)的发生。由于小檗碱在PanIN发育过程中可能会抑制糖酵解,所以我们测量了糖酵解的指标。定量逆转录聚合酶链反应和western blotting检测显示,小檗碱激活了腺苷单磷酸活化蛋白激酶(AMPK)通路。这表明小檗碱通过靶向关键代谢传感器AMPK抑制糖酵解。此外,小檗碱通过ampk -缺氧诱导因子1 α途径实现对PanIN的抑制。这些发现表明,小檗碱是预防CP向PanIN发展的潜在治疗候选者。
Most cases of pancreatic cancer develop in patients with chronic pancreatitis (CP). Berberine is natural product that exhibits anti-tumor effects in various types of cancer and is used in traditional Chinese medicine. In this study, we demonstrated that berberine inhibited the development of pancreatic intraepithelial neoplasia (PanIN) in anin vivoCP model and anin vitroacinar-to-ductal metaplasia model. As berberine may inhibit glycolysis during the development of PanIN, we measured indicators of glycolysis. Quantitative reverse transcription polymerase chain reaction and western blotting assays revealed that berberine activated the adenosine monophosphate-activated protein kinase (AMPK) pathway. This demonstrated that berberine suppressed glycolysis by targeting AMPK, a key metabolic sensor. Furthermore, berberine acted via the AMPK–hypoxia-inducible factor 1 alpha pathway to achieve suppression of PanIN. These findings show that berberine is a potential therapeutic candidate for preventing the progression of CP to PanIN.
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