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

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.

Keywords:

• Oesophageal cancer
• photodynamic therapy
• dihydroartemisinin
• glycolysis
• pyruvate kinase M2

Authors’ contributions

Mengru Jin is responsible for conceptualisation, methodology, formal analysis, investigation, writing- original draft and visualisation; Luyao Shi is responsible for investigation and data curation; Li Wang and Dingyuan Zhang are responsible for resources and writing- review and editing; Yanjing Li is responsible for writing-review and editing, supervision, project administration and fund acquisition. All authors read and approved the final manuscript.

Disclosure statement

The authors have no conflict of interest.

Additional information

Funding

This work was supported by Wu Jieping Medical Foundation (320.6750.2020–05-17), the Scientific Research Foundation of Harbin Medical University Cancer Hospital (JJZD2021-08 and JCQN2021-03) and Beijing Medical Award Foundation (YXJL-2023–0727-0159).