Tolerance of gastric cancer cells to 5-fluorouracil mediated by integrin αvβ6 through extracellular signal-regulated protein kinase / 中华消化外科杂志

ABSTRACT

Objective To explore the role of integrin αvβ6 in mediating the tolerance of gastric cancer AGS cells to 5-fluorouracil, and to determine whether direct β6-extracellular signal-regulated protein kinase(ERK) binding is involved. Methods Gastric cancer AGS cells in the logarithmic phase were incubated with either 5-fluorouracil for 24 hours ( control group), with 0.1 g/L of mouse anti-αvβ6 monoclonal antibody 10D5 for 6 hours and then with 5-fluorouracil for24 hours ( 10D5 group), with IgG2a and 5-fluorouracil ( IgG2a group), or with 5-fluorouracil and 20 μnol/L of ERK inhibitor PD98059 for 24 hours ( PD98059 group). Cell proliferation,apoptosis and the expression of Bcl-2 and caspase-3 protein were detected by MTT assay, flow cytometry and western blotting, respectively. All data were analysed by one-way analysis of variance and LSD test. Results The cell inhibition rates of the control group, 10D5 group, IgG2a group and PD98059 group were 28.1% ±2.7%,84.5% ± 1.6%, 31.4% ±5.2%, 86.7% ±5.2%, respectively, with a significant difference ( F = 342. 5, P ＜0.05). The apoptosis rates of the control group, 10D5 group, IgG2a group, and PD98059 group were 6.6% ±1.4%, 30.6% ± 2.4%, 8.1% ± 1.3%, 36.0% ±4.0%, respectively, with a significant difference among the four groups (F = 105.4, P ＜0.05 ). There was a significant difference in the expression of caspase-3 and Bcl-2 among the four groups (F=292.1, 181.6, P＜0.05). Conclusion Integrin αvβ6 can mediate the tolerance of gastric cancer AGS cells to 5-fluorouracil through direct β6-ERK binding.