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Monographic Report
Inhibitory effect of blocking both epidermal growth factor receptor and cyclooxygenase-2 pathway on proliferation of lung cancer A549 cells
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Abstract:
Objective:To explore the inhibitory effects of gefitinib (epidermal growth factor receptor inhibitor) combined with celecoxib (cyclooxygenase2 inhibitor) against human lung cancer A549 cells and the possible mechanism. :Methods: :A549 cells were cultured in RPMI 1640 medium and were divided into 4 groups: normal control group, 5 μmol/L gefitinib group, 25 μmol/L celecoxib group, and 5 μmol/L gefitinib+25 μmol/L celecoxib group. The morphological changes of A549 cells were observed under inverted microscope 48 h after treatment; the effects of drugs on growth of A549 Cells were detected by MTT assay; the apoptosis and cell cycles of A549 cells were measured by Annexin V/PI and Hoechst 33258 staining, respectively; and the expression of EGFR protein, COX2 protein, and EGFR mRNA were determined by immunofluorescence and realtime PCR. :Results: :Compared with gefitinib and celecoxib groups, many granules and vacuoles were observed in the gefitinib and celecoxib combination group, and cells became round and there was defluxion. Both gefitinib and celecoxib inhibited the growth of A549 cells in a time and dosedependent manner. After treatment for 48 h, the inhibitory rate was (58.2±4.6)% in the combination group, which was significantly higher than those of the other two groups. Apoptosis rate in the combination group was also significantly higher than those in the other two groups (33.9% vs 6.0%, 8.8%）, and the cell proportion in S phase significantly decreased and in G0/G1 phases significantly increased（P<0.01）. EGFR protein, COX2 protein, and EGFR mRNA expression in A549 cells was significantly decreased in the combination treatment group compared with those in the other two groups（P<0.05）. :Conclusion: :Gefitinib and celecoxib can synergistically inhibit the growth of A549 cells, possibly through promoting apoptosis, G0/G1 arrest, and downregulating activated EGFR and COX2 expression.
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Project Supported:
Supported by the Science and Technology Project of Shandong Province （No.ZR2009CM125）
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