期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

硼替佐米耐药多发性骨髓瘤细胞株KM3/BTZ的建立 被引量：3

Establishment of a bortezomib-resistant cell line KM3/BTZ of human multiple myeloma
原文传递
导出
摘要 目的建立人多发性骨髓瘤耐硼替佐米的细胞株,并对其生物学特性及耐药机制进行初步探讨。方法采用浓度梯度递增法,以人多发性骨髓瘤KM3细胞株为亲本,建立耐硼替佐米的多发性骨髓瘤细胞株,绘制生长曲线,并计算倍增时间;MTT法鉴定耐药细胞株的耐药性;RT-PCR方法检测MDR-1在亲代和耐药细胞株中的表达情况。结果成功建立耐硼替佐米的多发性骨髓瘤细胞株KM3/BTZ,耐药倍数为19.7倍。与亲代细胞相比,耐药细胞株倍增时间延长(P<0.05)。多药耐药相关基因MDR-1未参与耐药性的发生。结论成功建立人多发性骨髓瘤耐药细胞株KM3/BTZ,耐药性稳定,为研究耐药机制及逆转耐药提供了理想的模型。 Objective To establish a bortezomib-resistant cell line KM3/BTZ of human multiple myeloma （MM） and investigate its biological characteristics and mechanisms of drug-resistant in MM preliminarily. Methods The KM3 cell line was exposured to bortezomib at increasing doses to obtain a stable bortezomib-resistant KM3/BTZ in vitro. The growth curve was drawn and the doubling time was counted. MTT assay was used to evaluate the sensitivity of drug resistance. The expression of MDR-1 mRNA was determined by RT-PCR in KM3 and KM3/BTZ cell lines. Results The KM3/BTZ cell line resistant to bortezomib was established successfully with the resistance index of 19.7 （ KM3/ BTZ to KM3 ）. Compared with the parent cells, KM3/BTZ exhibited a significant longer doubling time （P 〈 0.05 ） . The expression of MDR-1 mRNA was not observed in either resistant or parent cells. Conclusion We have successfully established bortezomib resistance cell line KM3/BTZ and its drug-resistant character is stable. The KM3/BTZ cell line might serve as an ideal model to explore the drug-resistance mechanisms and to reverse the drug resistance.
作者 蒲业迪 李丽珍 马道新 董珂 赵川莉 宋强 王鲁群
机构地区 山东大学齐鲁医院血液科
出处 《山东大学学报（医学版）》 CAS 北大核心 2013年第2期33-36,43,共5页 Journal of Shandong University:Health Sciences
基金 山东省科技攻关课题基金(2008GG10002049)
关键词 硼替佐米 耐药 多发性骨髓瘤 细胞株 Bortezomib Drug resistance Multiple myeloma Cell line
分类号 R733.3 [医药卫生—肿瘤]
  • 相关文献

参考文献17

  • 1Rumpold H, Salvador C, Wolf A M, et al. Knockdown of P-gp resensitizes leukemic ceils to proteasome inhibitors [ J]. Biochemical and Biophysical Research Communica- tions, 2007, 361(2):549-554.
  • 2Oqawa Y, Tobinai K, Oqura M, et al. Phase I and 11 pharmacokinetic and pharmacodynamic study of the pro- teasome inhibitor bortezomib in Japanese patients with re- lapsed or refractory multiple myeloma[J]. Cancer Sci, 2008, 99(1) : 140-144.
  • 3Kumar S, Rajkumar S V. Many facts of bortezomib re- sistance/susceptibility[J]. Blood, 2008, 112 ( 6 ) : 2489- 2499.
  • 4张和君,郭仁.3例人骨髓瘤细胞株的建立[J].细胞生物学杂志,1988,2:88-89.
  • 5Snow k, Judd W. Characterisation of adriamycin and am- sacrine-resistant human leukaemic T cell lines [ J ]. Br J Cancer, 1991, 63 ( 1 ) : 17-28.
  • 6张蕈沐.抗肿瘤药物的药理与临床应用[M].郑州:河南医科大学出版社,1999:27-28.
  • 7Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer:drug resistance, apoptosis and survival signal[J]. Cancer Sci, 2003, 94(1 ) :15-21.
  • 8Eckford P D, Sharom F J. ABC effiux pump-based resist- ance to chemotherapy drugs [J]. Chem Rev, 2009, 109 (7) :2989-3011.
  • 9Mossink M H, van Zon A, Scheper R J, et al. Vaults : a ribonucleoprotein particle involved in drug resistance? [ J ]. Oncogene, 2003, 22 (47) :7458-7467.
  • 10Tsubaki M, Satou T, Itoh T, et al. Overexpression of MDR1 and survivin, and decreased Bim expression me- diate multidrug-resistance in multiple myeloma cells [J]. Leukemia Research, 2012, 36(10) : 1315-1322.

同被引文献32

  • 1Mitsiades N, Mitsiades CS, Poulaki V, et al. Molecular sequelae of proteasome inhibitionin human multiple mye- loma cells[J]. Proc Natl Acad Sci USA, 2002, 99(22) : 14374-14379.
  • 2Zheng B, Zhou R, Gong Y, et al. Proteasome inhibitor bortezomib overcomes P-gp-mediated multidrug resistance in resistant leukemia cell lines[J]. Biochemical Int J Lab Hematol, 2012, 34(3):237-247.
  • 3Palumbo A, Ambrosini MT, Benevolo G, et al. Borte- zomib, melphalan, prednisone, and thalidomide for re- lapsed multiple myeloma [ J ]. Blood, 2007, 109 ( 7 ) : 2767 -2772.
  • 4Berenson JR, Yang HH, Sadler K, et al. Phase I/I1 trial assessing bortezomib and melphalan combination therapy for the treatment of patients with relapsed or refractory multiple myeloma[J]. J Clin Oncol, 2006, 24(6) :937- 944.
  • 5Richardsom PG, Xie W, Jagannath S, et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma [J]. Blood, 2014, 123(10) :1461-1469.
  • 6Chanhan D, Li G, Shringarpure R, et al. Blockade of Hsp27 overcomes bortezomib/proteasome inhibitor PS- 341 resistance in lymphoma cells [ J ]. Cancer Res, 2003,63(69) :6174-6177.
  • 7Oerlemans R, Franke NE, Assaraf YG, et al. Molecular basis of bortezomib resistance: proteasome subunit beta5 (PSMB5) gene mutation and overexpression of PSMB5 protein[J]. Blood, 2008, 112(6) :2489-2499.
  • 8Carrasco DR, Sukhdeo K, Protopopova M, et al. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis [ J. Cancer Cell, 2007, 411 (4) :349-360.
  • 9Teru Hideshima, Klans Podar, Dharminder Chauhan, et al. p38 MAPK inhibition enhances PS-341 (borte- zomib)-induced cytotoxicity against multiple myeloma cells [ J ], Oncogene, 2004, 23 (54) : 8766-8776.
  • 10Wang BD, Kline CL, Pastor DM, et al. Prostate apop- tosis response protein 4 sensitizes human colon cancer cells to chemotherapeutic 5-FU through mediation of an NF kappaB and microRNA network [J]. Mol Cancer, 2010, 430(9) :1186-1476.

引证文献3

二级引证文献2

山东大学学报（医学版）
2013年 第2期

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