Zhu Wenhe, Zhang Wei, Xu Na, Li Yawei, Xu Junjie, Zhang Hong, Li Yan, Lv Shijie, Liu Wensen, Wang Huiyan
Jilin Medical University Jilin 132013 China
Institute of Military Veterinary Medicine, Academy of Military Medical Sciences Changchun 130122 China.
RSC Adv. 2018 Jun 6;8(37):20692-20700. doi: 10.1039/c8ra00565f. eCollection 2018 Jun 5.
Cancer cell promotion of glycolysis provides a promising therapeutic target for cancer treatment. Dihydroartemisinin (DHA) displays cytotoxicity to multiple human tumor cells. However, its effects on pancreatic cancer cells are not well studied. The objective of this study was to investigate the effect of DHA on glucose metabolism and cell viability in JF-305 pancreatic cancer cells. To achieve these goals, cell viability was measured with MTT assay, and the occurrence of apoptosis was detected. Glucose uptake, lactate production, and ATP content were measured. Western blotting was used for the detection of apoptosis-related protein expression. The result showed that DHA caused significant reduction in JF-305 cell viability, arrested the cell phase in G/M, induced apoptosis, and decreased the mitochondrial membrane potential and accumulated ROS. DHA also inhibited glucose uptake, lactate generation, and ATP production. Western blotting showed that treatment with DHA increased the activity of caspase-9 and caspase-3, downregulated Bcl-2 expression, and upregulated the expression levels of Bax and Cyto C. Meanwhile, DHA downregulated the Akt/mTOR signaling pathway and inhibited glucose transporter 1 expression. Our data suggest that DHA treatment increased the apoptosis of JF-305 pancreatic cancer cells, and the effect of apoptosis may be associated with the inhibition of glycolysis.
癌细胞促进糖酵解为癌症治疗提供了一个有前景的治疗靶点。双氢青蒿素（DHA）对多种人类肿瘤细胞具有细胞毒性。然而，其对胰腺癌细胞的作用尚未得到充分研究。本研究的目的是探讨DHA对JF-305胰腺癌细胞葡萄糖代谢和细胞活力的影响。为实现这些目标，采用MTT法检测细胞活力，并检测细胞凋亡的发生情况。测定葡萄糖摄取、乳酸生成和ATP含量。采用蛋白质免疫印迹法检测凋亡相关蛋白表达。结果表明，DHA导致JF-305细胞活力显著降低，使细胞周期停滞在G/M期，诱导细胞凋亡，并降低线粒体膜电位和积累活性氧。DHA还抑制葡萄糖摄取、乳酸生成和ATP产生。蛋白质免疫印迹法显示，DHA处理增加了caspase-9和caspase-3的活性，下调了Bcl-2表达，并上调了Bax和细胞色素C的表达水平。同时，DHA下调Akt/mTOR信号通路并抑制葡萄糖转运蛋白1表达。我们的数据表明，DHA处理增加了JF-305胰腺癌细胞的凋亡，且凋亡作用可能与糖酵解的抑制有关。
