Bufalin reverses resistance to gefitinib in xenografts of lung adenocarcinoma H 1975 cells in nude mice / 肿瘤

ABSTRACT

Objective: To investigate the effect of bufalin in combination with gefitinib on the growth of xenotransplants of lung adenocarcinoma H 1975 cells in nude mice, and to explore its possible mechanism. Methods: Forty nude mice bearing subcutaneous xenotransplants of lung adenocarcinoma H 1975 cells were randomly divided into four groups (in each group there were 10 nude mice) control group (no treatment), gefitinib-treated group, bufalin-treated group and bufalin in combination with gefitinib-treated group. Each group received corresponding intervention for 3 weeks. Tumor inhibitory rate was calculated. Apoptotic rate was measured by TUNEL staining method. The expression levels of EGFR-PI3K (epidermal growth factor receptor-phosphoinositide 3-kinase)/Akt signaling pathway-related proteins in xenografts were detected by Western blotting. Results: The tumor inhibitory rates of the control, gefitinib-treated, bufalin-treated and bufalin in combination with gefitinib-treated groups were 0%, 16.14%, 33.48% and 60.39%, respectively. The apoptotic rate of bufalin in combination with gefitinib-treated group was (75.8±3.16)%, which was significantly higher than those of the control group [(13.11 ± 1.60)%], gefitinib-treated group [(15.48±0.43)%] and bufalin-treated group [(45.09±3.81)%] (P < 0.01). The expression levels of phospho-EGFR, phospho-PI3K and phospho-Akt proteins were significantly reduced in group of bufalin in combination with gefitinib (P < 0.01). Conclusion: Bufalin in combination with gefitinib may block the EGFR-PI3K/Akt pathway to reverse the resistance to gefitinib in xenografts of lung adenocarcinoma H 1975 cells in nude mice. Copyright © 2013 by TUMOR.