Suppressed "Warburg Effect" in Nasopharyngeal Carcinoma Via the Inhibition of Pyruvate Kinase Type M2-Mediated Energy Generation Pathway.

Abstract

Warburg effect describes the abnormal energy metabolism in cancer cells and pyruvate kinase type M2 is involved in the regulation of this effect. In the current study, the role of pyruvate kinase type M2 in the initiation of Warburg effect in nasopharyngeal carcinoma cells was explored. The expression status of pyruvate kinase type M2 was detected in nasopharyngeal carcinoma samples and analyzed by different clinicopathological characteristics. Then the level of pyruvate kinase type M2 was suppressed in 2 nasopharyngeal carcinoma cell lines. The effects of pyruvate kinase type M2 inhibition on cell viability, apoptosis, invasion, glucose uptake, ATP generation, and glycolysis metabolism were determined. The data showed that the high expression of pyruvate kinase type M2 in nasopharyngeal carcinoma tissues was associated with the larger tumor size and advanced metastasis in the patients. The inhibition of pyruvate kinase type M2 resulted in the repressed proliferation and invasion in nasopharyngeal carcinoma cells, along with the increased apoptotic rate. The lack of pyruvate kinase type M2 function inhibited glucose uptake, while increased ATP generation in nasopharyngeal carcinoma cells. Moreover, the production of glycolysis metabolites, including pyruvic acid, lactate, citrate, and malate, was also suppressed by pyruvate kinase type M2 inhibition. At molecular level, the expressions of glucose transporter and hexokinase 2 were downregulated by pyruvate kinase type M2 inhibition, confirming the changes in glucose metabolism. Collectively, the current study demonstrated that the function of pyruvate kinase type M2 was important to maintain the proliferation and invasion of nasopharyngeal carcinoma cells, and the inhibition of the factor would antagonize nasopharyngeal carcinoma by blocking Warburg effect.