Dihydroartemisinin enhances the anti-tumour effect of photodynamic therapy by targeting PKM2-mediated glycolysis in oesophageal cancer cell.

IF 5.6 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Enzyme Inhibition and Medicinal Chemistry Pub Date : 2024-12-01 Epub Date: 2023-12-18 DOI:10.1080/14756366.2023.2296695

Mengru Jin, Luyao Shi, Li Wang, Dingyuan Zhang, Yanjing Li

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引用次数: 0

Abstract

Photodynamic therapy (PDT) has been demonstrated to provide immediate relief of oesophageal cancer patients' re-obstruction and extend their lifespan. However, tumour regrowth may occur after PDT due to enhanced aerobic glycolysis. Previous research has confirmed the inhibitory effect of Dihydroartemisinin (DHA) on aerobic glycolysis. Therefore, the current study intends to investigate the function and molecular mechanism of DHA targeting tumour cell aerobic glycolysis in synergia PDT. The combined treatment significantly suppressed glycolysis in vitro and in vivo compared to either monotherapy. Exploration of the mechanism through corresponding experiments revealed that pyruvate kinase M2 (PKM2) was downregulated in treated cells, whereas overexpression of PKM2 nullified the inhibitory effects of DHA and PDT. This study proposes a novel therapeutic strategy for oesophageal cancer through DHA-synergized PDT treatment, targeting inhibit PKM2 to reduce tumour cell proliferation and metastasis.

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双氢青蒿素通过靶向 PKM2 介导的食道癌细胞糖酵解增强光动力疗法的抗肿瘤效果

光动力疗法（PDT）已被证明能立即缓解食道癌患者的再梗阻，并延长他们的寿命。然而，由于有氧糖酵解作用增强，光动力疗法后可能会导致肿瘤再生。先前的研究证实了双氢青蒿素（DHA）对有氧糖酵解的抑制作用。因此，本研究旨在探讨 DHA 在协同 PDT 中靶向肿瘤细胞有氧糖酵解的功能和分子机制。与单一疗法相比，联合疗法能明显抑制体外和体内糖酵解。通过相应的实验探索其机制发现，丙酮酸激酶M2（PKM2）在治疗细胞中下调，而过表达PKM2则使DHA和PDT的抑制作用无效。本研究提出了一种新的食道癌治疗策略，即通过DHA协同PDT治疗，以抑制PKM2为靶点，减少肿瘤细胞的增殖和转移。

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来源期刊

Journal of Enzyme Inhibition and Medicinal Chemistry 医学-生化与分子生物学

CiteScore

10.30

自引率

10.70%

发文量

195

审稿时长

4-8 weeks

期刊介绍： Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.