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蟾毒灵逆转肺腺癌H1975细胞对吉非替尼耐药的体内实验研究
         
Bufalin reverses resistance to gefitinib in xenografts of lung adenocarcinoma H1975 cells in nude mice

摘    要
目的:观察蟾毒灵联合吉非替尼对肺腺癌H1975细胞裸鼠移植瘤生长的影响,并探讨其可能的作用机制。 方法:建立肺腺癌H1975细胞裸鼠皮下移植瘤模型(共40只)后,随机分为模型组(不进行药物干预)、吉非替尼组、蟾毒灵组及吉非替尼和蟾毒灵联合用药组(每组10只),分别用相应药物干预3周,计算肿瘤抑制率;应用TUNEL法检测移植瘤细胞凋亡,蛋白质印迹法检测移植瘤组织表皮生长因子受体-磷酯酰肌醇-3激酶(epidermal growth factor receptor-phosphoinositide 3-kinase,EGFR-PI3K)/Akt信号通路相关蛋白的表达。 结果:实验结束时,模型组、吉非替尼组、蟾毒灵组和联合用药组的抑瘤率分别为0%、16.14%、33.48%和60.39%。模型组、吉非替尼组、蟾毒灵组和联合用药组的移植瘤组织中肿瘤细胞凋亡率分别为(13.11±1.60)%、(15.48±0.43)%、(45.09±3.81)%和(75.8±3.16)%,联合用药组与模型组、吉非替尼组和蟾毒灵组比较,差异有统计学意义(P<0.01)。联合用药组移植瘤组织中p-EGFR、p-PI3K和p-Akt蛋白的表达水平明显下调(P<0.01)。 结论:蟾毒灵联合吉非替尼可逆转肺腺癌H1975裸鼠移植瘤对吉非替尼的耐药,其作用机制可能与阻断EGFR-PI3K/Akt信号通路有关。
标    签 肺肿瘤   抗药性   肿瘤   信号转导   蟾毒灵   吉非替尼   细胞   H1975   Lung neoplasms   Drug resistance   neoplasms   Signal transduction   Bufalin   Gefitinib   Cell   H1975  
 
Abstract
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 gefitinibtreated 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.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2013.04.002

 
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所属栏目 基础研究

基金项目 上海市浦东新区中医领军型人才培养项目(编号:PWZI2009-04)

收稿日期 2012/12/18

修改稿日期 2013/2/1

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引用该论文: KANG Xiao-hong,GONG Ya-bin,WANG Li-fang,WANG Zhong-qi,XU-Ling,XU Zhen-ye. Bufalin reverses resistance to gefitinib in xenografts of lung adenocarcinoma H1975 cells in nude mice[J]. Tumor, 2013, 33(4): 304~308
康小红,龚亚斌,王立芳,王中奇,许玲,徐振晔. 蟾毒灵逆转肺腺癌H1975细胞对吉非替尼耐药的体内实验研究[J]. 肿瘤, 2013, 33(4): 304~308


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