Abstract:

Objective  To study the effect of monotherapeutic, combinational and sequential applications of sunitinib and gemcitabine on the proliferation and apoptosis of human lung adenocarcinoma A549 cells and explore its mechanism. Methods  The cells were divided into the control group, sunitinib group, gemcitabine group, gemcitabine following sunitinib group, sunitinib following gemcitabine group, and combination group. After A549 cells were treated with monotherapeutic, combinational and sequential applications of sunitinib and gemcitabine, the cell growth inhibitory rate was measured by MTT assay; cellular apoptotic morphology changes were detected by Hoechst 33258 staining; cell cycle and apoptosis rate were evaluated by flow cytometry; the expressions of phosphorylation extracellular regulated protein kinase(P-ERK1/2) and phosphorylation protein kinase B (P-AKT) were detected by Western blotting. Results  A549 cells were resistant to sunitinib while sensitive to gemcitabine. The growth inhibitory and apoptosis rate in sunitinib following gemcitabine group were higher than those in gemcitabine group (P<0.05). Gemcitabine and sunitinib mainly blocked A549 cells on the S phase and G1 phase respectively. The cells in G1 phase of sunitinib following gemcitabine group increased while the cells in S phase decreased than those in the control group (P<0.05). Expressions of P-ERK1/2 and P-AKT were further inhibited in sunitinib following gemcitabine group than sunitinib group (P<0.05). Conclusion  The application of sunitinib following gemcitabine on A549 cells has synergistic effect. The mechanism is related to the expression of tyrosine kinase receptor signal pathway.

Key words: Sunitinib, Lung adenocarcinoma, Gemcitabine, K-RAS mutation