期刊文献+

V-ATPase在非小细胞肺癌中的表达及与耐药相关性的临床意义 被引量:5

Expression of Vacuolar-H+-ATPase in NSCLC and Its Correlation with Chemoresistance of NSCLC
暂未订购
导出
摘要 目的:探讨V-ATPase在非小细胞肺癌(NSCLC)中的表达及其在病理分类、分级中的差异性;检测相应癌组织对化疗药物的敏感性,分析其与V-ATPase表达的相关性,为进一步研究V-ATPase耐药性及其机制提供依据。方法:采用免疫组化EnVinsion法、免疫荧光法检测V-ATPase在92例NSCLC中的表达,激光共聚焦观察其定位,统计学分析差异性;用MTT法检测相应癌组织对化疗药物的敏感性,分析其与V-ATPase表达的相关性。结果:V-ATPase阳性表达主要定位于胞膜上和胞质中,鳞癌阳性率71.43%、腺癌阳性率83.72%,两者表达差异性非常显著(P=0.000);鳞癌Ⅱ阳性率58.33%、Ⅱ-Ⅲ阳性率84.00%,差异性显著(P=0.014);腺癌中高分化阳性率76.7%、低分化为100.0%,差异性显著(P=0.012)。环磷酰氨、吉西他滨、阿霉素、紫杉醇、顺铂化疗药在NSCLC组织中药物敏感性试验结果与其相应组织V-ATPase表达相关性检验,P值均<0.05,相关系数rs分别为-0.697、-0.654、-0.598、-0.216、-0.604,其中鳞癌中rs分别是-0.584、-0.512、-0.544、-0.269、-0.306,腺癌分别为-0.742、-0.607、-0.63、-0.349、-0.707。结论:V-ATPase在非小细胞肺癌中高表达,表达的高低与病理分类、分级有关,并很可能与NSCLC化疗药物耐药有关。 Objective: To investigate the expression of vacuolar-H +-ATPase (V-ATPase) protein in non-small cell lung cancer (NSCLC), to analyze the differences in V-ATPase expression among different pathological classifications and grades, and to explore the correlation of V-ATPase expression with the chemoresistance of NSCLC. Methods: We used immunohistochemistry and immunofluorescence to detect the expression of V-AT- Pase in 92 cases of NSCLC. The location of the protein was observed under light microscope and confocal laser scanning microscope. The chemoresistance of these cases was assayed by MTT method, and the corre- lation between the chemoresistance and V-ATPase expression in NSCLC were analyzed by statistics. Results: The V-ATPase protein was overexpressed at a rate of 71.43% in squamous cell lung cancer and 83.72% in lung adenocarcinoma, with a significant difference (P=0.000). In squamous cell lung cancer, the positive expression rates of pathological grade Ⅱ and Ⅱ-Ⅲ were 58.33% and 84.0%, respectively, with a statistical significance (P=0.014) The positive expression rates of moderately differentiated and low differentiated lung adenocarcinoma were 76.70% and 100.0%, respectively, with a significant difference (P=0.012). The P values of the correlation tests between the chemosensitivity of cyclophamide, gemcitabine, adriamycin, paclitaxel, or cisplatin and V-ATPase expression in the NSCLC were all less than 0.05. The correlation coefficients(rs) were-0.714,-0.687,-0.612,-0.33, and-0.67, respectively. Conclusion: The V-ATPase protein is overex- pressed in NSCLC at a higher expression rate in lung adenocarcinoma than in the squamous cell lung cancer. The chemoresistance of NSCLC is probably correlated with the V-ATPase expression.
出处 《中国肿瘤临床》 CAS CSCD 北大核心 2008年第22期1294-1298,共5页 Chinese Journal of Clinical Oncology
基金 陕西省科研攻关基金资助(编号:2004K13-G7)
关键词 非小细胞肺癌 V—ATPase 耐药性 药物敏感性 NSCLC V-ATPase Chemoresistance Chemosensitivity
  • 相关文献

参考文献12

  • 1李昌林,侯梅,赵宇,周清华.耐药基因相关蛋白在非小细胞肺癌组织中的表达及其临床意义[J].中国肺癌杂志,2005,8(6):523-526. 被引量:8
  • 2Huang Y,Sadee W. Membrane transporters and channels in chemoresistance mad-sensitivity of tumor cells[J]. Cancer Lett, 2006, 239(2): 168-182.
  • 3Albermann N, Schmitz-Winnenthal FH, Z'graggen K, et al. Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2,BCRP/ABCG2,and PX.R in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver[]]. Biochem Pharmacol, 2005, 70(6): 949-958.
  • 4Modok S, Mellor HR, CaUaghan R. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer[J]. Curr Opin Pharmacol, 2006, 6(4): 350-354.
  • 5Nakagawa H, Saito H, Ikegami Y, et al. Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer[J]. Cancer Lett, 2006, 234(1): 81-89.
  • 6Mahoney BP, Raghunand N, Baggett B, et al. Tumor acidity, ion trapping and chemotherapeutics. I. Acid pH affects the distribution of chemotherapeutic agents in vitro[J]. Biochem Pharmacol,2003, 66(7): 1207-1218.
  • 7Sennoune SR, Bakunts K, Martinez GM, et al. Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity[J]. AmJ Physiol Cell Physiol, 2004, 286(6): C1443-C1452.
  • 8Niikura K. Effect of a V-ATPase inhibitor, FR202126, in syngeneic mouse model of experimental bone metastasis[J]. Cancer Chemother Pharmacol, 2007, 60 (4): 555-562.
  • 9Breedveld P, Pluim D, Cipriani G, et al. The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models[]]. Mol Pharmacol, 2007, 71(1):240-249.
  • 10单树花,宋克敏,刘晶茹,徐函兵.磷饥饿下番茄幼苗根系液泡膜H^+-ATPase活性的适应性变化[J].植物生理与分子生物学学报,2006,32(6):685-690. 被引量:7

二级参考文献23

  • 1Kreisholt J,Sorensen M,Jensen PB,et al.Immunohistochemical detection of DNA topoisomerase Ⅱ alpha,P-glycoprotein and mul tidrug resistance protein (MRP) in small-cell and non-small-cell lung cancer.Br J Cancer,1998,77(9):1469-1473.
  • 2Tan B,Piwnica-Worms D,Ratner L.Multidrug resistance transporters and modulation.Curr Opin Oncol,2000,12(5):450-458.
  • 3Arai T,Yasuda Y,Takaya T,et al.Immunohistochemical expression of glutathione transferase-pi in untreated primary non-smallcell lung cancer.Cancer Detect Prey,2000,24(3):252-257.
  • 4Nishio K,Nakamura T,Koh Y,et al.Drug resistance in lung cancer.Curr Opin Oncol,1999,11(2):109-115.
  • 5Berger W,Elbling L,Hauptmann E,et al.Expression of the multidrug resistance-associated protein (MRP) and chemoresistance of human non-small-cell lung cancer cells.Int J Cancer,1997,73(1):84-93.
  • 6Scheper RJ,Broxterman HJ,Scheffer GL,et al.Overexpression of a M(r) 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance.Cancer Res,1993,53(7):1475-1479.
  • 7Chauncey TR.Drug resistance mechanisms in acute leukemia.Curr Opin Oncol,2001,13(1):21-26.
  • 8Oshika Y,Nakamura M,Tokunaga T,et al.Multidrug resistance-associated protein and mutant p53 protein expression in nonsmall cell lung cancer.Mod Pathol,1998,11(11):1059-1063.
  • 9Schroeijers AB,Scheffer GL,Reurs AW,et al.Detection of the Mr 110,000 lung resistance-related protein LRP/MVP with monoclonal antibodies.J Histochem Cytochem,2001,49 (11):1379-1385.
  • 10Trussardi A,Poitevin G,Gorisse MC,et al.Sequential overexpression of LRP and MRP but not P-gp 170 in VP16-selected A549 adenocarcinoma cells.Int J Oncol,1998,13(3):543-548.

共引文献15

同被引文献61

引证文献5

二级引证文献5

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部