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乔利罂粟酮 B 通过抑制 Akt/mTOR 通路使非小细胞肺癌细胞中己糖激酶 2 的表达下调,从而抑制糖酵解。

Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non-small cell lung cancer cells.

机构信息

Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University, Kaifeng, P.R. China.

Minsheng College, Henan University, Kaifeng, P.R. China.

出版信息

J Cell Biochem. 2018 Jun;119(6):4967-4974. doi: 10.1002/jcb.26742. Epub 2018 Mar 9.

Abstract

Jolkinolide B (JB), a bioactive compound isolated from herbal medicine, has been found to inhibit tumor growth by altering glycolysis. However, whether glycolysis is influenced by JB in non-small cell lung cancer (NSCLC) cells and the mechanism remain unknown. The aim of the present study was to evaluate the effect of JB on the glycolysis in NSCLC cells and the underlying molecular mechanism. The results showed that JB treatment inhibited cell viability of A549 and H1299 cells in a concentration-dependent manner. JB reduced the glucose consumption, lactate production, and HK2 expression. The expressions of p-Akt and p-mTOR were also decreased by JB treatment. Knockdown of HK2 reduced glucose consumption and lactate production. Inhibition of the Akt/mTOR pathway decreased HK2 expression and inhibited glycolysis. In conclusion, the results indicated that JB inhibits glycolysis by down-regulating HK2 expression through inactivating the Akt/mTOR pathway in NSCLC cells, suggesting that JB might be a potential therapeutic agent for the treatment of NSCLC.

摘要

乔利酮 B(JB)是从草药中分离得到的一种具有生物活性的化合物,已被发现通过改变糖酵解来抑制肿瘤生长。然而,JB 是否会影响非小细胞肺癌(NSCLC)细胞中的糖酵解以及其机制尚不清楚。本研究旨在评估 JB 对 NSCLC 细胞糖酵解的影响及其潜在的分子机制。结果表明,JB 处理以浓度依赖性方式抑制 A549 和 H1299 细胞的活力。JB 降低葡萄糖消耗、乳酸生成和 HK2 表达。JB 处理还降低了 p-Akt 和 p-mTOR 的表达。HK2 的敲低减少了葡萄糖消耗和乳酸生成。抑制 Akt/mTOR 通路降低了 HK2 表达并抑制了糖酵解。综上所述,研究结果表明,JB 通过抑制 Akt/mTOR 通路使 HK2 表达下调从而抑制 NSCLC 细胞中的糖酵解,提示 JB 可能是治疗 NSCLC 的潜在治疗剂。

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