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08.02.2020 | Original Article

The influence of photodynamic therapy on the Warburg effect in esophageal cancer cells

Lasers in Medical Science
Junqing Gan, Shumin Li, Yu Meng, Yuanyu Liao, Mingxia Jiang, Ling Qi, Yanjing Li, Yuxian Bai
Wichtige Hinweise
Junqing Gan and Shumin Li contributed equally to this work.

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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.

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