期刊文献+

β-Catenin信号转导通路在肺癌A549细胞顺铂耐药中的作用 被引量:2

The Role of β-Catenin Pathway on DDP Resistance in Human Lung Cancer A549 Cell
下载PDF
导出
摘要 目的建立肺癌A549顺铂多药耐药细胞株,研究肺癌耐药的机制。方法使用顺铂逐步增加剂量和间歇大剂量冲击相结合的方法诱导肺癌A549细胞,以建立其多药耐药细胞株A549/DDP;MTT细胞毒实验比较A549与A549/DDP细胞对顺铂的敏感性;绘制A549和A549/DDP细胞生长曲线,观察二者的增殖速度变化;Western blotting实验显示A549和A549/DDP细胞之间Akt、p-Akt、GSK-3β、p-GSK-3β和β-Catenin蛋白的表达改变。结果经过30周的诱导我们建立了肺癌A549细胞的顺铂耐药细胞株A549/DDP;MTT细胞毒实验结果显示顺铂对A549和A549/DDP细胞的IC50值分别为(1.37±0.09)和(11.63±0.74)μmol/L,与A549细胞比较,A549/DDP细胞对顺铂耐药8.47倍,生长曲线结果显示A549/DDP细胞的增殖速度与A549细胞没有显著性差异;Western blotting的结果显示A549/DDP细胞的Akt磷酸化水平升高,抑制了下游GSK-3β的活性,导致了细胞内β-Catenin蛋白的上调。结论建立了肺癌A549顺铂多药耐药细胞系A549/DDP,A549/DDP细胞中β-Catenin通路的激活与其耐药性的形成有一定的相关性。 Objective To establish a cisplatin (DDP) resistance A549 cell line and to explore the mechanisms of multidrng resistance in human lung cancer. Methods The human cancer A549 cells were exposed in gradually increasing or interval high dose of DDP. MTr assay was used to detect the cytotoxic activity of DDP against A549 and A549/DDP cells. Cell numbers were calculated to draw growth curve. The protein expressions of Akt, p -Akt, GSK -3β, p- GSK - 3β and β -Catenin were determined by western blotting analysis in A549 and A549/DDP cells. Results DDP resistance cell line AS49/DDP was established by DDP continuous iriducing. The IC50 values of DDP against A549 and A549/DDP cells were ( 1.37 ± 0. 09 ) and ( 11.63 ± 0. 74 ) μmol/L by MTI7 assay respectively. The cells growth curve showed that cell proliferation had no significant difference between A549 and A549/DDP cells. Western blotting analysis showed that phospho - Akt was up - regulated in A549/DDP cells, which elevated the phosphorylation of GSK - 3β at sefine 9. Compared to A549 cells, the up - regulation of β - Catenin protein was found in A549/DDP cells. Conclusions A549/DDP showed resistant to DDP and was a reliable muhidrug resistance cell model. The β - Catenin pathway played an important role in the resistant phenotype of A549/DDP cell line.
作者 陶黎阳 龙捷
出处 《辽宁医学院学报》 CAS 2011年第1期6-8,12,共4页 Journal of Liaoning Medical University (LNMU) Bimonthly
基金 2010年度广州医学院博士 留学回国人员基金项目 编号:2010C17
关键词 肺癌 A549细胞 多药耐药 β—Catenin信号通路 lung cancer A549 cell multidrng resistance β- Catenin pathway
  • 相关文献

参考文献12

  • 1Jemal A,Siegel R,Xu J,et al.Cancer statistics[J].CA Cancer J Clin,2010,60(5):277-300.
  • 2Lage H.An overview of cancer multidrug resistance:a still unsolved problem[J].Cell Mol Life Sci,2008,65(20):3145-3167.
  • 3Stewart DJ.Tumor and host factors that may limit efficacy of chemotherapy in non-small cell and small cell lung cancer[J].Crit Rev Oncol Hematol,2010,75(3):173-234.
  • 4陈杰,白春学,钱桂生,黄桂君.A549/CDDP多药耐药细胞系的建立[J].中国癌症杂志,2003,13(2):186-187. 被引量:17
  • 5Jones RJ,Matsui WH,Smith BD.Cancer stem cells:are we missing the target[J].J Natl Cancer Inst,2004,96(8):583-585.
  • 6Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics[J].CA Cancer J Clin,2005,55(1):74-108.
  • 7周向东,钱桂生,刘凌志.人小细胞肺癌SH77多药耐药细胞系的建立及其生物学特征分析[J].第三军医大学学报,2003,25(16):1405-1407. 被引量:6
  • 8Eramo A,Lotti F,Sette G,et al.Identification and expansion of the tumorigenic lung cancer stem cell population[J].Cell Death Differ,2008,15(3):504-514.
  • 9Donnenberg VS,Donnenberg AD.Multiple drug resistance in cancer revisited:the cancer stem cell hypothesis[J].Journal of Clin Pharmacol,2005,45(8):872.
  • 10He B,Barg RN,You L,et al.Wnt signaling in stem cells and non-small-cell lung cancer[J].Clin Lung Cancer,2005,7(1):54-60.

二级参考文献7

共引文献21

同被引文献40

  • 1王红军,廖新华,崔飞博,魏光兵.siRNA阻断NF-κB信号通路抑制胃癌SGC-7901细胞的增殖及侵袭[J].西安交通大学学报(医学版),2012,33(4):466-469. 被引量:3
  • 2张晔,田昕,刘云鹏,曲秀娟,杨向红,侯科佐,滕月娥,张敬东.蟾蜍灵对顺铂耐药胃癌SGC7901细胞增殖与凋亡的影响及其作用机制[J].西安交通大学学报(医学版),2012,33(4):498-500. 被引量:14
  • 3Schwarzenbach H. Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP,and the lung-resistance pro- tein LRP in multiple myeloma[J]. Med Oncol, 2002,19 (2) : 87- 104.
  • 4Zhang W,Shi Y,Chen Y, et al. Enhanced antitumor efficacy by paclitaxel loaded pluronic P123/F127 mixed micelles against non- small cell lung cancer based on passive tumor targeting and mod- ulation of drug resistanee[J]. Eur J Pharm Biopharm, 2010, 75(3) :341-53.
  • 5Breedveld P, Beninen JH, Schellens JHM. Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS pen- etration of anticancer drugs [J]. Trends PharmacoI Sci, 2006, 27(1) :17-24.
  • 6Loe DW, Deeley RG, Cole SP. Biology o5 the muhidrug resist ance-associated protein,MRP[J]. Eur J Cancer, 1996,32A(6) : 945-957.
  • 7Zuben E. Sauna, Suresh V. Ambudkar. About a switch: how P-gly- coprotein(ABCB1) harnesses the energy of ATP binding and hy- drolysis to do mechanical work[ J]. Mol Cancer Ther, 2007,6(1) : 13-23.
  • 8Shi Hongcan, LU Dan, Shu Yusheng, et al. Expression of multidrug resistance-related proteins p-glycoprotein, glutathione-s-transferas- es,topoisomerase-II and lung resistance protein in primary gastric cardiac adenocarcinoma [ J ]. Hepato-gastroenterology, 2008, 55 (86-87) : 1530-1536.
  • 9吴吴.芍药苷抑制NF-xB活性对人胃癌细胞增殖、凋亡的影响及其机制研究[D].南京:南京医科大学,2008.
  • 10Jianhua Wang, Yuesheng Xia, Huan Wang, et al. Chinese Herbs of Shenghe Powder Reverse Multidrug Resistance of Gastric Car- cinoma SGC-7901 [ J]. Integr Cancer Ther, 2007,6(4) :400-404.

引证文献2

二级引证文献6

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