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Archive > Volume 23 Issue 6 > 2016,23(6):759-765. DOI:10.3872/j.issn.1007-385X.2016.06.004 Prev Next
Basic Research
Two-deoxy glucose enhances killing efficacy of cisplatin on human melanoma cells and its mechanism
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Abstract:
Objective:To explore effect of drug combination of 2-deoxy glucose (2-DG) and cisplatin on apoptosis of human melanoma cells and its mechanism. Methods: MTT assay was used to detect viability of the cells; Annexin-V/PI staining and flow cytometry assay detected apoptosis of the cells and Wetern blotting assay detected expressions of related-apoptosis protein. Intracellular ATP content was detected by a bioluminescence kit. Results: Although cisplatin with variou concentrations (5-25 μmol/L) alone inhibited viability of the A375 cells as concentration and time dependenct patterns, cisplatin (except 5 μmol/L) combined with 2-DG (10 μmol/L) all enhanced inhibition effect on viability of the cells. Single 2-DG (10 μmol/L) did not induce apparent death of the A375 cells (<10%), single cisplatin (20 μmol/L) resulted in death of the cells (about 50%) and both of them resulted in death of the cells (>80%), compairing with single drug groups there was a significant difference (P<0.01). Single cisplatin or combination with 2-DG all induced cleavages of Caspase-3 and PARP-1, and inhibited expression of anti-apoptosis protein Mcl-1. Two-DG combined with cisplatin (20 μmol/L) could significantly inhibit expression of hexokinase Ⅱ and content of intracellular ATP was lower than that in the control group (6.3 μmol/mg protein vs 33 μmol/mg protein), that was siginificantly different from those of single drug groups (P<0.01). Two-DG combined with cisplatin did not introduce apoptosis of nornal human melanocytes. In addition, the combination of both drugs also enhanced activity of killing another three human melanoma cells (SK-100, C8161 and Mum-2C). Conclution: Two-DG could specifically enhance susceptibility of cisplatin to induce apoptosis of human melanoma cells, Its mechanism could relate with down-regulating expression of anti-apoptosis protein Mcl-1 as well as inhibiting level of tumor hexokinase and synthesis of ATP.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No.81241148), and the Science and Technology Plan of Dalian (No.2014E14SF147)
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