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核仁磷酸蛋白和c-Src在耐药肺腺癌细胞中的表达及其与化疗耐药之间的关系
         
Expressions of nucleophosmin and c-Src in drug-resistant lung adenocarcinoma and its relationship with chemotherapy resistance

摘    要
目的: 观察核仁磷酸蛋白(nucleophosmin, NPM)和c-Src蛋白在耐药肺腺癌细胞中的表达及其与化疗敏感性之间的关系。方法: 通过顺铂浓度梯增渐进式给药法筛选出不同程度的肺腺癌耐药细胞,并将其接种于小鼠皮下。实验分为4组:对照组(小鼠皮下接种耐0.0μg/mL顺铂的Lewis肺癌细胞)、非耐药组(小鼠皮下接种耐0.0μg/mL顺铂的Lewis肺癌细胞)、低耐药组(小鼠皮下接种耐10.0μg/mL顺铂的Lewis肺癌细胞)和高耐药组(小鼠皮下接种耐20.0μg/mL顺铂的Lewis肺癌细胞)。对照组小鼠腹腔注射0.9%氯化钠溶液,非耐药组、低耐药组和高耐药组小鼠腹腔注射顺铂(4 mg/kg)进行化疗,观察小鼠皮下移植瘤的生长情况和肺转移情况,应用免疫组织化学法、蛋白质印迹法和实时荧光定量PCR法检测小鼠皮下移植瘤组织中NPM和c-Src蛋白及mRNA的表达。结果: 非耐药组、低耐药组和高耐药组小鼠皮下移植瘤的体积和质量均小于对照组(P值均<0.01),非耐药组、低耐药组和高耐药组的抑瘤率分别为73.23%、51.45%和32.74%。低耐药组和高耐药组小鼠皮下移植瘤组织中NPM和c-Src mRNA及蛋白的表达水平均高于非耐药组和对照组(P值均<0.01),高耐药组小鼠皮下移植瘤组织中NPM和c-Src mRNA及蛋白的表达水平均高于低耐药组(P值均<0.01),而非耐药组与对照组小鼠皮下移植瘤组织中NPM和c-Src mRNA及蛋白表达水平之间的差异无统计学意义(P值均>0.05)。结论: NPM和c-Src在耐药的Lewis肺癌细胞中表达上调,可能与肺腺癌细胞对顺铂耐药有关。
标    签 肺肿瘤   化学疗法   辅助   抗药性   肿瘤   核仁磷酸蛋白   c-Src   Lung neoplasms   Chemotherapy   adjuvant   Drug resistance   neoplasm   Nucleophosmin   c-Src  
 
Abstract
Objective: To investigate the expressions of nucleophosmin (NPM) and c-Src in resistant lung adenocarcinoma and its relationship with chemotherapy resistance. Methods: After filtering out different degrees of pulmonary adenocarcinoma cells resistant to cisplatin by method of delivery increased cisplatin concentration, the cells were inoculated subcutaneously into mice. Then the cells were divided into four groups:control group (Lewis pulmonary carcinoma cells resistant to 0.0 μg/mL cisplatin were inoculated subcutaneously into mice), non-resistant group (Lewis pulmonary carcinoma cells resistant to 0.0 μg/mL cisplatin were inoculated subcutaneously into mice), low resistance group (Lewis pulmonary carcinoma cells resistant to 10.0 μg/mL cisplatin were inoculated subcutaneously into mice) and high resistance group (Lewis pulmonary carcinoma cells resistant to 20.0 μg/mL cisplatin were inoculated subcutaneously into mice). The mice in the control group were intraperitoneally injected with 0.9% NaCl, while the mice in non-resistant group, low resistance group and high resistance group were intraperitoneally injected with cisplatin (4 mg/kg). The growth of xenografted tumor in mice and lung metastasis were observed. The expressions of NPM and c-Src protein and mRNA in xenografted tumor tissues in different groups were detected by immunhistochemistry, Western blotting and real-time fluorescent quantitative PCR, respectively. Results: The volume and weight of xenografted tumor in non-resistant group, low resistance group and high resistance group were lower than those in the control group (all P<0.01). The tumor inhibition rates of non-resistant group, low resistance group and high resistance group were 73.23%, 51.45% and 32.74%, respectively. The expression levels of NPM and c-Src protein and mRNA in xenografted tumor tissues of low resistance group and high resistance group were higher than those of non-resistant group and the control group (all P<0.01). The expression levels of NPM and c-Src protein and mRNA in xenografted tumor tissues of high resistance group were higher than those of low resistance group (all P<0.01), whereas the expression levels of NPM and c-Src protein and mRNA in xenografted tumor tissues were not significantly different between non-resistant group and the control group (all P>0.05). Conclusion: The expressions of NPM and c-Src in resistant Lewis pulmonary carcinoma cells are up-regulated, which may be involved in resistance to cisplatin of lung adenocarcinoma.

中图分类号 R734.2   DOI 10.3781/j.issn.1000-7431.2016.11.145

 
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所属栏目 基础研究

基金项目 湖南省医药卫生科研计划项目(编号:B2013-157)

收稿日期 2016/2/22

修改稿日期 2016/4/7

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引用该论文: HE Jianbin,LIU Lijing,XIANG Zhi,YI Gaozhong,ZHANG Ping. Expressions of nucleophosmin and c-Src in drug-resistant lung adenocarcinoma and its relationship with chemotherapy resistance[J]. Tumor, 2016, 36(6): 613~620
贺兼斌,刘理静,向志,易高众,张平. 核仁磷酸蛋白和c-Src在耐药肺腺癌细胞中的表达及其与化疗耐药之间的关系[J]. 肿瘤, 2016, 36(6): 613~620


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