[Cytotoxic effect of epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in combination with oxaliplatin on lung cancer cell line A549].

Background & Objective: ZD1839, a selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has clinical antitumor activity, but its efficacy is low. This study was to assess the effects of ZD1839 in combination with oxaliplatin on lung adenocarcinoma cell line A549, and to provide pre-clinical evidence for optimizing the schedule of oxaliplatin combined with ZD1839.
Methods: Chou and Talalay method was used to analyze the combination effects of sequencing ZD1839 and oxaliplatin on A549 cells. Cell cycle distribution and cell apoptosis were analyzed by flow cytometry. The effects of oxaliplatin combined with ZD1839 on the proliferation of A549 cells in nude mice were also evaluated.
Results: Sequential oxaliplatin followed by ZD1839 produced synergistic effect, with a combination index (CI) of 0.51+/-0.01. In contrast, ZD1839 followed by oxaliplatin exhibited antagonist effect, with a CI of 1.56+/-0.03. Compared with other sequences, oxaliplatin followed by ZD1839 induced more cells being arrested in G(2/M) phase (37.9%, P<0.05); the apoptosis rate was 22.3%. The inhibition rate of tumor growth in nude mice was 58.9% when treated with oxaliplatin followed by ZD1839, 52.4% when treated with oxaliplatin and ZD1839 for 24 h and followed by ZD1839 for additional 48 h, and 30.6% when treated with ZD1839 followed by oxaliplatin.
Conclusion: Sequential oxaliplatin followed by ZD1839 has the maximal inhibitory effect on the proliferation of A549 cells.