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钾离子通道蛋白Kir2.1/KCNJ2及多药耐药蛋白MRP1/ABCC1在小细胞肺癌中的表达及相关性
引用本文:刘换新,吴晓霞,张燕,郭琳琅. 钾离子通道蛋白Kir2.1/KCNJ2及多药耐药蛋白MRP1/ABCC1在小细胞肺癌中的表达及相关性[J]. 中国病理生理杂志, 2013, 29(11): 1940-1945. DOI: 10.3969/j.issn.1000-4718.2013.11.004
作者姓名:刘换新  吴晓霞  张燕  郭琳琅
作者单位:1南方医科大学附属珠江医院病理科,广东广州 510282; 2武警广东总队医院病理科, 广东 广州 510507
基金项目:国家自然科学基金资助项目(No.81172241)
摘    要: 目的:探讨内向整流钾通道2.1(Kir2.1/KCNJ2)及多药耐药相关蛋白1(MRP1/ABCC1)在小细胞肺癌(SCLC) 中的表达情况及两者的相关性。方法:采用实时定量PCR和蛋白印迹法检测小细胞肺癌多药耐药细胞株H69AR及敏感株H69细胞中Kir2.1/KCNJ2及MRP1/ABCC1 mRNA和蛋白的表达水平,采用免疫组化EnVision两步法检测44 例SCLC组织中Kir2.1/KCNJ2和MRP1蛋白的表达水平;采用蛋白免疫共沉淀实验检测Kir2.1/KCNJ2与MRP1/ABCC1之间的相互作用。
结果:H69AR细胞株中Kir2.1/KCNJ2及MRP1/ABCC1 mRNA和蛋白的表达均显著高于H69细胞株,二者均有显著差异(P<005);免疫组化结果表明SCLC组织中Kir2.1/KCNJ2和MRP1/ABCC1阳性表达率分别为47.7%(21/44) 和52.3%(23/44),两者表达在SCLC 中呈正相关(r=0853,P<0.01); Kir2.1/KCNJ2与MRP/ABCC1在H69AR细胞内可形成复合物。结论:Kir2.1/KCNJ2与小细胞癌多药耐药有关。Kir2.1/KCNJ2和MRP1/ABCC1之间可能存在共同作用通路。Kir2.1/KCNJ2可能通过调控MRP1/ABCC1的表达促进SCLC多药耐药的发生。

关 键 词:小细胞肺癌  内向整流钾通道  多药耐药相关蛋白1  免疫共沉淀  
收稿时间:2013-03-25

Clinical significance of Kir2.1/KCNJ2 and MRP1/ABCC1 protein expression in small-cell lung cancer
LIU Huan-xin,WU Xiao-xia,ZHANG yan,GUO Lin-lang. Clinical significance of Kir2.1/KCNJ2 and MRP1/ABCC1 protein expression in small-cell lung cancer[J]. Chinese Journal of Pathophysiology, 2013, 29(11): 1940-1945. DOI: 10.3969/j.issn.1000-4718.2013.11.004
Authors:LIU Huan-xin  WU Xiao-xia  ZHANG yan  GUO Lin-lang
Affiliation:1Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; 2Department of Pathology, Guangdong Provincial Corps Hospital of Chinese People’s Armed Police Forces, Guangzhou 510507, China.
Abstract:AIM: To investigate the expression of inward rectifying potassium channel 2.1 (Kir2.1/KCNJ2) and multidrug resistance-associated protein 1 (MRP1/ABCC1) in small-cell lung cancer (SCLC), and the correlation between them. METHODS:The mRNA and protein expression of MRP1/ABCC1 and Kir2.1/KCNJ2 in H69 and H69AR cell lines was detected by real-time PCR and Western blotting. Immunohistochemistry (EnVision) method was used to detect the expression of Kir2.1/KCNJ2 and MRP1/ABCC1 proteins in 44 cases of SCLC tissues. The interaction of Kir2.1/KCNJ2 with MRP1/ABCC1 was tested by co-immunoprecipitation (co-IP). RESULTS:The mRNA and protein expression of MRP1/ABCC1 and Kir2.1/KCNJ2 in H69AR cells was all significantly higher than that in H69 cells (P<005). The positive expression rates of Kir2.1/KCNJ2 and MRP1/ABCC1 in the 44 cases of SCLC tissues were 47.7% (21/44) and 52.3% (23/44), respectively. A positive correlation was found between the expression of Kir2.1/KCNJ2 and MRP1/ABCC1 in SCLC tissues (r=0.853, P<0.01). Co-IP results showed that Kir2.1/KCNJ2 could bind MRP1/ABCC1 in H69AR cells. CONCLUSION: Kir2.1/KCNJ2 is related to the multidrug resistance of SCLC. Kir2.1/KCNJ2 and MRP1/ABCC1 may have common function roles. Therefore, Kir2.1/KCNJ2 may promote the multidrug resistance of SCLC by regulating the expression of MRP1/ABCC1.
Keywords:Small-cell lung cancer  Inwardly rectifying potassium channels  Multidrug resistance-associated protein 1  Co-immunoprecipitation
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