AB65. Biological effects and mechanism of abnormal expression of FBP2 in gastric cancer

Background: Increasing evidences suggest that cancer is a metabolic disease. Here, we investigated the potential role of fructose-1,6-bisphosphatase-2 (FBP2), the enzyme that catalyses the hydrolysis of fructose-1, 6-bisphosphate to fructose-6-phosphate and inorganic phosphate in glucose metabolism in the development of gastric cancer (GC).

Methods: The expression of FBP2 in GC was evaluated. The biological function was determined by MTT assay, colony formation, and flow cytometric analysis through ectopic expressing FBP2 in gastric cancer cell lines coupled with in vivo study. The methylation status was analyzed by Mass array, BGS, and MSP. To explore the biological behaviors of FBP2 in GC, FBP2 was overexpressed by plasmid transfection, and MTT, soft agar and nude mice model were used.

Results: Our data indicated that FBP2 was downregulated in GC tissues (86.2%, 100/116), and absent or low FBP2 expression in GC tissues was correlated with poor survival of GC patients (P=0.019). Conversely, ectopic expression of FBP2 in GC cells activated AMP-activated protein kinase (AMPK) signalling, inhibited the Akt-mTOR pathway, suppressed glucose metabolism, enhanced apoptosis, and reduced cell proliferation. Bisulphite genomic sequencing (BGS) in gastric cancer cell lines revealed that the FBP2 promoter region was densely methylated, and treatment of GC cells with the demethylation reagent, 5-aza-2-deoxycytidine (5-Aza), led to an increase in FBP2 expression. Importantly, forced expression of FBP2 abrogated tumour formation of these GC cells in nude mice.

Conclusions: Our results indicate that FBP2 does negatively regulate cell growth, and reduced expression of FBP2 that may contribute to carcinogenesis for GC. These findings suggest that restoration of FBP2 expression can be a promising strategy for the treatment of GC.

Keywords: Fructose-1,6-bisphosphatase-2 (FBP2); glycolysis; gastric cancer; cell growth; prognosis