期刊文献+

联合应用p38MAPK抑制剂对降低结肠癌阿霉素耐药性的影响 被引量:1

Use of p38 MAPK inhibitor reduces resistance of colon cancer cells to doxorubicin
暂未订购
导出
摘要 目的:探讨p38 MAPK抑制剂通过Akt(蛋白激酶B)有关的信号途径对结肠癌细胞阿霉素(Doxorubicin)化疗敏感性的影响.方法:应用阿霉素(Dox)和p38 MAPK特异性抑制剂SB203580及两者联合应用去处理结肠癌HCT-116细胞株.采用MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]法检测化疗药物对肿瘤细胞的生存抑制率,Western blot蛋白免疫印迹技术检测化疗药物处理后癌细胞Akt和磷酸化Akt的表达水平.结果:MTT显示阿霉素和抑制剂SB203580对结肠癌细胞均有抑制作用(26.60%,33.87%),后者大于前者,两者相同用量联合后癌细胞抑制率更明显(56.04%).Western blot显带说明阿霉素处理组较联合组的Akt表达水平并无明显差异,而磷酸化的Akt水平较SB203580组和联合组显著升高.亦即抑制剂组和联合组方案可降低结肠癌细胞磷酸化Akt的表达水平.结论:p38 MAPK抑制剂SB203580可能通过阻断P13K/Akt信号途径或其他有关Akt的通路以提高结肠癌细胞阿霉素化疗的敏感性. AIM:To evaluate whether SB203580,a p38MAPK inhibitor,reduces resistance of colon cancer HCT116 cells to doxorubicin and to explore possible mechanisms involved.METHODS:Doxorubicin alone or in combination with SB203580 was used to treat subcultured HCT-116 cells.After treatment,cell growth was determined by MTT assay,and Akt and p-AKt expression was detected by Western blotting.RESULTS:Either doxorubicin or SB203580 inhibited HCT-116 cell growth,and the latter had a stronger inhibitory effect than the former (26.60% vs 33.87%).Combined use of doxorubicin and SB203580 had more strong inhibitory effect than treatment with either of them alone (56.04%).Expression of Akt showed no significant difference between cells treated with doxorubicin alone and those treated with combined doxorubicin and SB203580,while the phosphorylation of Akt was significantly higher in the doxorubicin group than in the combination group.CONCLUSION:The p38 MAPK inhibitor SB203580 could block the Akt signaling pathways and increase the sensitivity of colon cancer cells to doxorubicin.
出处 《世界华人消化杂志》 CAS 北大核心 2012年第2期145-148,共4页 World Chinese Journal of Digestology
关键词 阿霉素 P38 MAPK抑制剂 结肠癌 抗耐药性 Doxorubicin p38MAPK inhibitor Colon cancer Anti-resistance
  • 相关文献

参考文献17

  • 1Lin R,Shi Ng L,Wang CH.In vitro study of anticancer drug doxorubicin in PLGA-based microparticles.Biomaterials2005;26:4476-4485.
  • 2艾耀伟,于红刚,于皆平,杨艳,李欢,胡晓雯.磷脂酰肌醇3′-激酶通路活化对化疗药物诱导的胃癌细胞凋亡的影响[J].中华内科杂志,2007,46(7):588-589. 被引量:5
  • 3Cabane C,Coldefy AS,Yeow K,Dérijard B.The p38pathway regulates Akt both at the protein and transcriptional activation levels during myogenesis.Cell Signal2004;16:1405-1415.
  • 4Lee ER,Kim JY,Kang YJ,Ahn JY,Kim JH,Kim BW,Choi HY,Jeong MY,Cho SG.Interplay between PI3K/Akt and MAPK signaling pathways in DNAdamaging drug-induced apoptosis.Biochim Biophys Acta2006;1763:958-968.
  • 5Fresno Vara JA,Casado E,de Castro J,Cejas P,Belda-Iniesta C,González-Barón M.PI3K/Akt signalling pathway and cancer.Cancer Treat Rev2004;30:193-204.
  • 6Poh TW,Pervaiz S.LY294002and LY303511sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the phosphoinositide3-kinase-Akt pathway.Cancer Res2005;65:6264-6274.
  • 7张利,于红刚,于皆平,罗和生.P13K/Akt/p27kip1通道介导胃癌细胞对阿霉素、足叶乙甙化疗的耐药性及其机制[J].世界华人消化杂志,2008,16(6):575-581. 被引量:4
  • 8李小毛,肖兰,杨越波,沈慧敏,曾海涛,王泽华.SB203580与雷帕霉素联合对人子宫内膜癌Ishikawa细胞的体外抗肿瘤作用[J].广东医学,2009,30(1):26-28. 被引量:4
  • 9Ogunwobi O,Mutungi G,Beales IL.Leptin stimulates proliferation and inhibits apoptosis in Barrett's esophageal adenocarcinoma cells by cyclooxygenase-2-dependent,prostaglandin-E2-mediated transactivation of the epidermal growth factor receptor and c-Jun NH2-terminal kinase activation.Endocrinology2006;147:4505-4516.
  • 10Yang SY,Miah A,Sales KM,Fuller B,Seifalian AM,Winslet M.Inhibition of the p38MAPK pathway sensitises human colon cancer cells to5-fluorouracil treatment.Int J Oncol2011;38:1695-1702.

二级参考文献58

  • 1戴春岭,符立梧.肿瘤多药耐药逆转剂的研究进展[J].中国药理学通报,2005,21(5):513-518. 被引量:39
  • 2李军华,于皆平,于红刚,刘晋,罗和生.蛋白激酶B、Caspase-9通路活化对胃癌细胞生长及化疗敏感性的影响[J].中华消化杂志,2006,26(1):2-5. 被引量:2
  • 3徐细明,于皆平,戈伟,罗和生,于红刚.Wortmannin预处理增强胃癌细胞对阿霉素敏感性的研究[J].中华消化杂志,2006,26(1):51-53. 被引量:5
  • 4严婷,张莲芬,张熔熔,冯磊,金坚.人乳腺癌多药耐药细胞系MCF-7/MDR^a的建立及其生物学特性的初步研究[J].细胞生物学杂志,2006,28(4):591-595. 被引量:14
  • 5FINGAR D C, BLENIS J. Target of rapamycin (TOR) : an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression[ J]. Oncogene, 2004, 23(18) : 3 151 -3 171.
  • 6STEPHAN S, DATrA K, WANG E, et al . Effect of Rapamycin alone and in combination with antiangiogenesis therapy in an orthotopic model of human pancreatic cancer [J]. Clin Cancer Res, 2004, 10(20) : 6 993 -7 000.
  • 7BOFFA D J, LUAN F, THOMAS D, et al. Rapamycin inhibits the growth and metastatic progression of non - small cell lung cancer[J]. Clin Cancer Res, 2004, 10 (1 Pt 1) : 293 -300.
  • 8RATHMELL W K, WRIGHT T M, RINI B I. Molecularly targeted therapy in renal cell carcinoma[ J ]. Expert Rev Anticancer Ther, 2005, 5(6): 1 031 -1 040.
  • 9JANUS A, ROBAK T, SMOLEWSKI P. The mammalian target of the rapamycin (mTOR) kinase pathway : its role in tumourigenesis and targeted antitumour therapy[ J]. Cell Mol Biol Lett, 2005, 10 : 479 - 498.
  • 10LUAN F L, DING R, SHARMA V K, et al. Rapamycin is an effective inhibitor of human renal cancer metastasis[ J]. Kidney Int, 2003, 63(3) : 917 -926.

共引文献36

同被引文献5

  • 1Humtsoe JO, Kramer RH. Differential epidermal growth factor receptor signaling regulates anchorage-independent growth by modulation of the PI3K/AKT pathway [J]. Oncogene, 2010,29(8): 1214-1226.
  • 2Chang L, Karin M. Mammalian MAP kinase signalling cascades [ J]. Nature, 2001,410(6824) : 37-40.
  • 3Hilger RA, Scheulen ME, Strumberg D. The Ras-Raf-MEK-ERK pathway in the treatment of cancer [ J ]. Onkologle, 2002,25 ( 6 ) : 511-518.
  • 4Raman M, Chen W, Cobb MH. Differential regulation and properties of MAPKs [ J ]. Oncogene, 2007,26 ( 22 ) : 3100-3112.
  • 5Rengifo-Cam W, Umar S, Sarkar S, et al. Autiapoptotic effects of progastrin on pancreatic cancer cells are mediated by sustained activation of nuclear factor-{ kappa } B [ J]. Cancer Res, 2007, 67 ( 15 ) : 7266-7274.

引证文献1

二级引证文献1

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