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Inhibitory effects of sodium dichloroacetate combined with cisplatin on gastric cancer cells
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Abstract:
Objective:To explore the anti-tumor effect of dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, on gastric cancer cells in vitro.Methods: Gastric cancer cell SGC-7901 and BGC-823 lines cultured in vitro were treated respectively by different concentrations of DCA for 24 h. Viability rates of the gastric cancer cells were evaluated by MTT assay. The synergistic effect of DCA combined with cisplatin (DDP) on the gastric cancer cells was analyzed with the median effect principle. Invasive ability of the gastric cancer cells were then evaluated by Transwell assay. Their apoptotic rates were measured by double staining flow cytometry. Results:DCA (20, 40, 60, 80 and 100 mmol/L) remarkably reduced survival rates of the gastric cancer cells (SGC-7901and BGC-823) in a concentration-dependent manner. The IC50 of DCA for 24 h in SGC-7901 and BGC-823 cells were 60.9 mmol/L and 53.8 mmol/L, respectively. Small-concentrations of DCA (20, 40 mmol/L) in combination with DDP (5, 10 μmol /L) synergistically reduced cell viability in the gastric cancer cells, their combination index was less than 1 both. Compared to control group, the number of invaded SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly decreased (\[99.3±11.7\], \[55.7±60\] and \[38.3±6.7\] vs \[182.7±17.3\], P<0.05\]; the number of invaded BGC-823 cells in the same concentrations of DCA groups also significantly decreased (\[88.7±8.3\], \[49.0±5.7\] and \[42.3±6.7\] vs \[170.7±15.0\], P<0.05\]. In addition, the early apoptotic rates of the SGC-7901 cells in 60, 80 and 100 mmol/L DCA groups significantly increased (\[31.7±5.2\]%, \[35.0±5.4\]%, \[37.8±62\] vs \[8.1±1.3\]%, P<0.05, compared to control group); while the early apoptotic rates of the BGC-823 cells in the same concentrations of DCA groups also significantly increased ( \[24.6±4.6\]%, \[31.9±42\]%, \[40.4 ±5.7\]% vs \[6.6±1.4\]%, P<0.05, compared to control group). Conclusion:DCA can obviously inhibit survial of gastric cancer cells cultrued in vitro, and produce a asynergistic effect with chemotherapetric agents. DCA can inhibit invasiveness of gastric cancer cells and induce their apoptosis. Targeting pyruvate dehydrogenase kinase may be a novel therapuetic method of gastric carcinoma in future.
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Project Supported:
Project supported by the Natural Science Foundation of Gansu (No. 145RJZA036), and the Foundation of the First Hospital of Lanzhou University（No.ldyyynjx201112）
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