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外泌体在体外对乳腺癌细胞耐药信息传递的作用 被引量:21
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作者 许乘凤 杨振林 +5 位作者 花义同 程凯 滕晓飞 张英哲 刘健 王晓红 《西安交通大学学报(医学版)》 CAS CSCD 北大核心 2017年第2期193-198,220,共7页
目的探讨外泌体(exosomes,EXOs)在乳腺癌细胞间耐药信息的传递作用。方法选用乳腺癌敏感细胞株(MCF-7)及其阿霉素耐药株(MCF-7/ADR)为模型,用超速离心法提取MCF-7/ADR外泌体(ADR/EXO);用透射电子显微镜观察鉴定细胞外泌体形态;运用倒置... 目的探讨外泌体(exosomes,EXOs)在乳腺癌细胞间耐药信息的传递作用。方法选用乳腺癌敏感细胞株(MCF-7)及其阿霉素耐药株(MCF-7/ADR)为模型,用超速离心法提取MCF-7/ADR外泌体(ADR/EXO);用透射电子显微镜观察鉴定细胞外泌体形态;运用倒置荧光显微镜观察ADR/EXO与MCF-7细胞的相互作用过程;运用激光共聚焦显微镜观察MCF-7与MCF-7/ADR在Transwell小室共培养60h后细胞内阿霉素药物浓度变化;运用CCK-8法检测ADR/EXO与MCF-7细胞共培养后对阿霉素的IC50的影响;运用RT-PCR检测MCF-7与ADR/EXO共培养后MDR1基因表达水平的变化;运用Western blot法检测MCF-7与ADR/EXO共培养12h和72h后P-gp表达水平的变化。结果透射电子显微镜下,外泌体呈现典型的圆形或椭圆形杯口状结构,直径为40~100nm;用PKH67标记ADR/EXO显示,ADR/EXO是可以被MCF-7细胞摄取;与ADR/EXO共培养后敏感细胞株MCF-7对阿霉素的IC50耐药性升高2.62倍,差异有统计学意义(P<0.05);经过与MCF-7/ADR在Transwell小室中共培养60h后的MCF-7细胞,胞内可见阿霉素聚集减少,核区分布减少,荧光强度减弱;MCF-7+ADR/EXO组MDR1的mRNA表达量明显增加,是MCF-7组的8.69倍,差异有统计学意义(P<0.05);与MCF-7组相比,共培养12h的MCF-7+ADR/EXO组P-gp相对表达量升高4.64倍,差异有统计学意义(P<0.05);与MCF-7组相比,共培养72h的MCF-7+ADR/EXO组P-gp相对表达量升高3.37倍,差异有统计学意义(P<0.05)。结论乳腺癌外泌体可能具有传递耐药信息的作用,耐药细胞外泌体能够使敏感细胞获得一定的耐药性,耐药细胞外泌体向敏感细胞传递P-gp,不仅可以通过蛋白形式进行传递,而且可以通过mRNA的形式进行传递。 展开更多
关键词 外泌体 乳腺癌 耐药p-gp
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The expression and significance of the multidrug resistance-related proteins P-gp, MRP and LRP in human non-small cell lung cancer tissues 被引量:1
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作者 Yun Zuo Jianan Huang +1 位作者 Chuanyong Mu Dong Shen 《The Chinese-German Journal of Clinical Oncology》 CAS 2007年第5期432-436,共5页
Objective: To explore the expression and significance of the multidrug resistance-related proteins P-glycopro-tein (P-gp), multidrug resistance-related protein (MRP), lung resistance protein (LRP) in human non-small c... Objective: To explore the expression and significance of the multidrug resistance-related proteins P-glycopro-tein (P-gp), multidrug resistance-related protein (MRP), lung resistance protein (LRP) in human non-small cell lung cancer (NSCLC) tissues and paratumor tissues. Methods: Immunohistochemistry (IHC) was used to examine the expression level of proteins P-gp, MRP and LRP in 43 samples of NSCLC and 15 samples of paratumor tissues. Results: The expression rates of P-gp, MRP and LRP in 43 tumor tissues were 74.42% (32/43), 67.44% (29/43) and 88.37% (38/43), respectively, while in 15 paratumor tissues were 13.33% (2/15), 20.00% (3/15) and 6.67% (1/15), respectively. There was significant difference in the expression of proteins (P-gp, MRP and LRP) between lung cancer tissues and paratumor tissues (P < 0.05). The expres-sion of proteins P-gp, LRP in lung adenocarcinoma were higher than that in other pathological carcinomas (P < 0.05). The expression of protein MRP was not related to pathological type, clinical stage and classification of histodifferentiation (P > 0.05). Conclusion: Multidrug resistance is more common in NSCLC. The proteins of P-gp, MRP and LRP participated in the formation of multidrug resistance in lung cancer. Detection of multidrug resistance-related proteins in lung cancer tissues may be useful to choice drugs. 展开更多
关键词 non-small cell lung cancer (NSCLC) chemotherapy multidrug resistance (MDR) p-gp MRP LRP
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Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells 被引量:6
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作者 Hai-chang Zhang Fei Zhang +4 位作者 Bing Wu Jing-hua Han Wei Ji Yan Zhou Rui-fang Niu 《Clinical oncology and cancer researeh》 CAS CSCD 2012年第2期99-104,共6页
Objective To explore the interaction of Anxa2 with P-Glycoprotein (P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA ... Objective To explore the interaction of Anxa2 with P-Glycoprotein (P-gp) in the migration and invasion of the multidrug-resistant (MDR) human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA (shRNA) targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells (P〈0.05). There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells. 展开更多
关键词 P-GLYCOPROTEIN Anxa2 drug resistance MULTIPLE neoplasm metastasis breast neoplasm
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p-gp170和ki-67在口腔鳞癌中的表达 被引量:3
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作者 潘树矿 方梅 《中华全科医学》 2014年第7期1068-1070,共3页
目的口腔鳞癌临床最多见的是高、中分化程度的鳞癌,低度分化极为罕见,癌细胞的增殖活性和对化疗药物的耐药性与愈后关系紧密,多药耐药糖蛋白p-gp170和人抗增殖核细胞抗原ki-67较具代表性,检测多药耐药糖蛋白p-gp170和人抗增殖核细胞抗原... 目的口腔鳞癌临床最多见的是高、中分化程度的鳞癌,低度分化极为罕见,癌细胞的增殖活性和对化疗药物的耐药性与愈后关系紧密,多药耐药糖蛋白p-gp170和人抗增殖核细胞抗原ki-67较具代表性,检测多药耐药糖蛋白p-gp170和人抗增殖核细胞抗原ki-67在不同分化的口腔鳞癌中的表达,以探讨二者与口腔鳞癌分化程度的关系。方法采用免疫组织化学SP法检测p-gp170和ki-67在41例高分化和17例中分化口腔鳞癌中的表达,p-gp170在高、中分化的口腔鳞癌表达关系采用χ2检验,ki-67在高、中分化的口腔鳞癌表达关系采用秩和检验。结果 p-gp170在高分化和中分化鳞癌之间的关系应用卡方检验的方法进行相关分析,χ2值为15.172,P值为0.001,差异有统计学意义;ki-67高分化组平均值为5.40,中分化组为10.34,ki-67采用秩和检验,Z值为-3.567,P值为0.000,差异有统计学意义。结论口腔鳞癌恶性程度越高,耐药指标多药耐药糖蛋白p-gp170的表达水平越高,其增殖指标人抗增殖核细胞抗原ki-67表达水平越高,二者呈正相关。 展开更多
关键词 糖蛋白p-gp170 人抗增殖核细胞抗原ki-67 口腔鳞状细胞癌
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