The effects of gefitinib combined with curcumin on proliferation of human lung adenocarcinoma cell A549/H1975

ZHANG Nan; LIU Gui-yang; DONG Ning

doi:10.3969/j.issn.1672-8157.2013.03.006

Abstract：Objective: To observe the effects of gefitinib combined with curcumin on proliferation of human lung adenocarcinoma cell A549(EGFR wild;K-ras mutation)and H1975(EGFR mutation:T790M+L858R;K-ras wild), and the impact of curcumin on the concentration of gefitinib in cell membrane. Methods:Using complete medium, gefitinib and curcumin were diluted into five different concentrations, and cross-over concentrations of gefitinib and curcumin were combined for culturing A549/H1975 cells for 72 h. Cell proliferation was assayed by MTT method. The dose-effect of gefitinib combined with curcumin was evaluated by combination index (CI). The CI value less than 1 indicates that the combination protocol has a synergistic effect. HPLC-MS was used to detect the concentration of gefitinib in cell membrane. Results:The results indicated that cell proliferation of A549 cells was markedly inhibited by combination of gefitinib and curcumin, which showed synergistic and forceful additive effect. While there was only additive effect on H1975 cells. When the concentration of gefitinib was 1μmol·L-1, adding curcumin increased concentration of gefitinib in A549 cell membrane to (1.25±0.26) times compared with the single gefitinib group, with significant difference between the two groups(P<0.05). Otherwise, there was not obvious diversification with or without curcumin on A549 cell cultured with 10μmol·L-1 of gefitinib or H1975 cells. Conclusion:Proliferation of A549 cells was significantly inhibited by combination of curcumin and low-dose gefitinib, but the effect on H1975 cells was not proving satisfactory, which possibly resulted from the elevated concentration of gefitinib in A549 cell membrane by means of adding curcumin.