The influence of photodynamic therapy on the Warburg effect in esophageal cancer cells
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ORIGINAL ARTICLE
The influence of photodynamic therapy on the Warburg effect in esophageal cancer cells Junqing Gan 1 & Shumin Li 1 & Yu Meng 1 & Yuanyu Liao 1 & Mingxia Jiang 1 & Ling Qi 1 & Yanjing Li 1
&
Yuxian Bai 1
Received: 3 September 2019 / Accepted: 13 January 2020 # Springer-Verlag London Ltd., part of Springer Nature 2020
Abstract To investigate whether the Warburg effect is a key modulator on the resistance mechanism of photodynamic therapy (PDT). Glycolysis was examined by the test of lactate product and glucose uptake at different post-PDT time points. Cell viability was detected by the CCK-8 assay and cell proliferation was detected by colony formation assay. The expression of glycolysis and related proteins were examined by western blotting. Target gene was silenced by RNAi. In the present study, we assessed the effect of PDT on cancer cell glycolysis. Our team has demonstrated that pyruvate kinase M2 (PKM2), a key speed-limiting enzyme of glycolysis, was significantly overexpressed in patients with esophageal cancer. Our results in the present study showed that PKM2 was downregulated, and lactate product and glucose uptake were inhibited in cells exposed to 5-aminolevulinic acid (5-ALA)–mediated PDT at 4 h after treatment. However, at 24 h after PDT, we observed a substantial increase in PKM2 expression, lactate product, and glucose uptake. Moreover, silencing of PKM2 gene abrogated the upregulatory effect of PDT on glycolysis at late post-PDT period. 2-Deoxy-D-glucose (2-DG) is a recognized chemical inhibitor of glycolysis. The combined treatment of 2-DG and PDT significantly inhibited tumor growth in vitro at 24 h. These results demonstrate that PDT drives the Warburg effect in a time-dependent manner, and PKM2 plays an important role in this progress, which indicated that PKM2 may be a potential molecular target to increase the sensitivity of esophageal cancer cells to PDT. Keywords Esophageal cancer . Photodynamic therapy . Warburg effect . Pyruvate kinase M2 . 2-Deoxy-D-glucose
Introduction Esophageal cancer is the eighth most common form of malignancy worldwide and the fourth leading cause of all cancer deaths in China [1–3]; although with extensive research, improvement in surgical techniques, and the introduction of multimodal therapies [2], it still has poor prognosis and high mortality rate. Therefore, innovative approaches are urgently needed. Photodynamic therapy (PDT), mediated by a photosensitizer and visible light of the appropriate wavelength, results in
Junqing Gan and Shumin Li contributed equally to this work. * Yanjing Li [email protected] * Yuxian Bai [email protected] 1
Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang, China
the production of reactive oxygen species (ROS) that can destroy tumor cells directly through apoptotic or necrotic pathways, or indirectly by harming the vasculature tissue inside and outside the tumor to stimulate hypoxia and starvation of tumor cells, which in turn causes tumor
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