Inhibitory effect of γ-aminobutyric acid on proliferation of colorectal cancer cells and its chemosensitization
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Abstract:
Objective:To explore the inhibitory effect of γ-aminobutyric acid (GABA) on colorectal cancer cells (SW480 and HCT116 lines) and its chemosensitization. Methods: The effects of GABA and its combination with anticancer drugs 5-fluorouracil (5-FU) or oxaliplatin (OXA) on proliferation of colorectal cancer cells (SW480, HCT116) were determined using CCK-8 assay; the effects of GABA on cell cycles of SW480 and CT116 were analyzed using Flow cytometry assay; the tumor weight and size were investigated in experiment of tumor-bearing nude mice; the expression of Ki67 protein in cancer tissues of the nude mice and the apoptosis of colorectal cancer cells in the nude mice were observed using immunohistochemistry and TUNEL staining assays respectively; the effect of GABA combined with OXA on growth of the tumor cells was observed with experiment in vivo. Results: GABA (100 μmol/L) significantly inhibited the proliferation of SW480 and HCT116 cells, their inhibition rates were (37.38±262)% and (15.54±1.33)%, respectively. Further increasing of the GABA concentration to 200 μmol/L did not obviously enhance the inhibitory rate. GABA decreased the number of SW480 and HCT116 cells at S phase by 11.8% and 10.7%, respectively. Inhibitory rates of the ISW480 cell in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA groups (combined with 5-FU: \[72.76±1.07\]% vs \[63.82±3.29\]%, q=4.079, P<005; combined with OXA: \[65.60±1.19\]% vs \[57.09±1.25\]%, q=4.128, P<0.05); inhibitory rates of HCT116 cells in GABA combined with 5-FU or OXA groups were higher than those in 5-FU or OXA alone groups (combined with 5-FU: \[79.53±1.12\]% vs \[69.71±009\]%, q=4.569, P<0.05; combined with OXA: \[73.19±0.07\]% vs \[64.65±199\]%, q=4.561, P<005). At end of the experiment, the tumor weight and size of the nude miceinthe combined group of GABA and OXA were significantly lower than those in control group and the oxaliplatin alone group (\[0.20±0016\] g vs \[0.42±0.039\] g, \[0.36±0.030\]g; \[250±27\] mm3 vs \[780±60\] mm3, \[520±46\] mm3, P<0.01). The combination of GABA with OXA also significantly inhibited the expression of Ki67 protein in the tumor tissues and promoted apoptosis of the tumor cells in tumor tissues. Conclusion: GABA couldhave strong inhibitory effect on proliferation of the colorectal cancer cells and its combination use with 5-FU or OXA could enhance efficacy of chemotherapy.
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Project supported by the National Natural Science Foundation of China(No.81472770)