Effect of mannose on the radiosensitivity of six non-small cell lung cancer cell lines
Ge Hong1, Luo Hui1, Liu Kangdong2, Jia Xuechao2, Nie Wenna2, Zhang Qiqi2, Lu Bingbing2, Yang Ran2, Wang Nan1, Song Shuai1, Jiao Ruidi1
1Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China; 2Sino-American Hormel Cancer Institute, Zhengzhou 450003, China
Abstract：Objective To investigate the effect of mannose on the radiosensitivity of six human non-small cell lung cancer cell lines and its possible mechanism. Methods The expression of mannose phosphate isomerase in six lung cancer cell lines were detected by Western blot. The inhibitory effect of mannose on the proliferation of lung cancer cell lines were observed by MTT assay. When irradiated with 0, 2, 4, 6, 8 and 10Gy, the effect of mannose on the radiosensitivity of six lung cancer cell lines was detected by plate clone formation assay, respectively;and the apoptosis rates of normal control, mannose, irradiation and combined groups were detected by flow cytometry. Results The expression levels of mannose phosphate isomerase were different among six lung cancer cell lines. Among them, A549 cells had the highest expression level and H460 cells showed the lowest expression level. When aDministrated with 11.1 mmol/L mannose, the same inhibitory effect was observed on both A549 and H460 cell lines. Moreover, the inhibitory effect on H460 cell line was significantly increased with the increase of mannose concentration. In addition, aDministration of 11.1 mmol/L mannose could significantly increase the radiosensitivity and apoptosis rate of H460 cell line. However, it exerted limited effect upon the radiosensitivity and apoptosis rate of A549 cell line. Conclusion In six lung cancer cell lines with high expression of mannose phosphate isomerase, the aDministration of mannose can enhance the radiosensitivity of partial tumors cells.
Ge Hong,Luo Hui,Liu Kangdong et al. Effect of mannose on the radiosensitivity of six non-small cell lung cancer cell lines[J]. Chinese Journal of Radiation Oncology, 2020, 29(7): 558-562.
[1] Thorens B, Mueckler M. Glucose transporters in the 21st century[J]. Am J Physiol Endocrinol Metab, 2010, 298(2):E141-145. DOI:10.1152/ajpendo.00712.2009. [2] DeRossi C, Bode L, Eklund EA, et al. Ablation of mouse phosphomannose isomerase (mpi) causes mannose 6-phosphate accumulation, toxicity, and embryonic lethality[J]. J Biol Chem, 2006, 281(9):5916-5927. DOI:10.1074/jbc. M511982200. [3] Zhang D, Chia C, Jiao X, et al. D-mannose induces regulatory t cells and suppresses immunopathology[J]. Nat Med, 2017, 23(9):1036-1045. DOI:10.1038/nm.4375. [4] Schneider A, Thiel C, Rindermann J, et al. Successful prenatal mannose treatment for congenital disorder of glycosylation-ia in mice[J]. Nat Med, 2011, 18(1):71-73. DOI:10.1038/nm.2548. [5] Milandri R, Maltagliati M, Bocchialini T, et al. Effectiveness of d-mannose, hibiscus sabdariffa and lactobacillus plantarum therapy in prevention of infectious events following urodynamic study[J]. Urologia, 2018:86(3):122-125. DOI:10.1177/0391560318 798291. [6] White L, Ma J, Liang S, et al. Lc-ms/ms determination of d-mannose in human serum as a potential cancer biomarker[J]. J Pharm Biomed Anal, 2017, 137(1):54-59. DOI:10.1016/j.jpba.2016.12.017. [7] Gonzalez PS, O'Prey J, Cardaci S, et al. Mannose impairs tumour growth and enhances chemotherapy[J]. Nature, 2018, 563(7733):719-723. DOI:10.1038/s41586-018-0729-3. [8] Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism[J]. Nat Rev Cancer, 2011, 11(2):85-95. DOI:10.1038/nrc2981. [9] Warburg O. On the origin of cancer cells[J]. Science, 1956, 123(3191):309-314. DOI:10.1126/science.123.3191.309. [10] Icard P, Shulman S, Farhat D, et al. How the warburg effect supports aggressiveness and drug resistance of cancer cells?[J]. Drug Resist Updat, 2018, 38(1):1-11. DOI:10.1016/j.drup.2018.03.001. [11] Patra KC, Wang Q, Bhaskar PT, et al. Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer[J]. Cancer Cell, 2013, 24(2):213-228. DOI:10.1016/j.ccr.2013.06.014. [12] Hitosugi T, Zhou L, Elf S, et al. Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth[J]. Cancer Cell, 2012, 22(5):585-600. DOI:10.1016/j.ccr.2012.09.020. [13] Westphal V, Kjaergaard S, Davis JA, et al. Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type ⅠB:long-term outcome and effects of mannose supplementation[J]. Mol Genet Metab, 2001, 73(1):77-85. DOI:10.1006/mgme.2001.3161. [14] Sattler UG, Meyer SS, Quennet V, et al. Glycolytic metabolism and tumour response to fractionated irradiation[J]. Radiother Oncol, 2010, 94(1):102-109. DOI:10.1016/j.radonc.2009.11.007. [15] Shen H, Hau E, Joshi S, et al. Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism[J]. Mol Cancer Ther, 2015, 14(8):1794-1804. DOI:10.1158/1535-7163.mct-15-0247. [16] Leung E, Cairns RA, Chaudary N, et al. Metabolic targeting of hif-dependent glycolysis reduces lactate, increases oxygen consumption and enhances response to high-dose single-fraction radiotherapy in hypoxic solid tumors[J]. BMC Cancer, 2017, 17(1):418. DOI:10.1186/s12885-017-3402-6.
2020, Vol. 29 
