Mannose enhances the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis

Hui Luo,Qinfu Dan,Xiaohui Wang,Yunhan Wang,Hong Ge

doi:10.1007/s12672-021-00447-0

Abstract

BackgroundTo investigate the effect of mannose on radio-sensitivity of human esophageal squamous cell carcinoma (ESCC) cell line and its possible mechanism.MethodsThe expression of mannose phosphate isomerase (MPI) in human esophageal cancer cell lines were detected by Western blot. The inhibitory effect of mannose on human esophageal cancer cell lines were observed by MTT assay. Plate clone formation assay was performed to investigate the efficacy of mannose on radio-sensitivity of human esophageal cancer cells. The apoptosis rates of tumor cells treated with mannose and/or radiation therapy was calculated by flow cytometry. Furthermore, we analyzed intracellular metabolites using liquid chromatography mass spectrometry to identify selective sugar metabolites.ResultsMPI expression was various in human esophageal cancer cells. KYSE70 cells was associated with the highest MPI expression whereas KYSE450 cells had the lowest MPI expression level. When administrated with 11.1 mM/L mannose, the same inhibitory effect was observed in both KYSE70 and KYSE450 cell lines. Moreover, the inhibitory effect was significant on KYSE450 cell lines with an increased mannose concentration. The application of 11.1 mM/L mannose could significantly enhance the radio-sensitivity of KYSE450 cell line; and tumor cell apoptosis rate was also increased. However, there was limited efficacy of mannose on the radio-sensitivity and apoptosis rate of KYSE70 cell line. Additionally, intracellular metabolites analyzation revealed that glycolysis could be disturbed by mannose when combined with radiation therapy in esophageal cancer cells.ConclusionIn esophageal cancer cell lines with low MPI expression, the administration of mannose was associated with enhanced radio-sensitivity.

Highlights

Mannose was an isomer of glucose, and belonged to one type of monosaccharide
KYS450 was associated with the lowest expression of mannose phosphate isomerase (MPI), whereas KYSE70 was correlated with the highest expression of MPI (Fig. 1A, B); SHEE cell line was associated with low MPI expression
Our results suggested that mannose inhibits cell proliferation in a dose-dependent manner, especially in cells with low MPI expression (KYSE450 and SHEE) (Fig. 1C)

Summary

Introduction

Mannose was an isomer of glucose, and belonged to one type of monosaccharide. It was naturally existing in a free state. Methods The expression of mannose phosphate isomerase (MPI) in human esophageal cancer cell lines were detected by Western blot. The inhibitory effect of mannose on human esophageal cancer cell lines were observed by MTT assay. Plate clone formation assay was performed to investigate the efficacy of mannose on radio-sensitivity of human esophageal cancer cells. The application of 11.1 mM/L mannose could significantly enhance the radio-sensitivity of KYSE450 cell line; and tumor cell apoptosis rate was increased. There was limited efficacy of mannose on the radio-sensitivity and apoptosis rate of KYSE70 cell line. Intracellular metabolites analyzation revealed that glycolysis could be disturbed by mannose when combined with radiation therapy in esophageal cancer cells. Conclusion In esophageal cancer cell lines with low MPI expression, the administration of mannose was associated with enhanced radio-sensitivity

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