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《Tumor》 2013-04
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Bufalin reverses resistance to ge tinib in xenografts of lung adenocarcinoma H1975 cells in nude mice

KANG Xiao-hong 1, 2 , GONG Ya-bin 1 , WANG Li-fang 1 , WANG Zhong-qi 1 , XU-Ling 1 , XU Zhen-ye 1 1. Department of Medical Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; 2. Department of Clinical Oncology, Pingdingshan First People’s Hospital, Pingdingshan 467000, He’nan Province, China  
Objective:To investigate the effect of bufalin in combination with gefitinib on the growth of xenotransplants of lung adenocarcinoma H1975 cells in nude mice, and to explore its possible mechanism. Methods:Forty nude mice bearing subcutaneous xenotransplants of lung adenocarcinoma H1975 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 H1975 cells in nude mice.
【Fund】: 上海市浦东新区中医领军型人才培养项目(编号:PWZI2009-04)
【CateGory Index】: R734.2;R285.5
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【Citations】
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