期刊文献+

2-甲氧基雌二醇增强骨髓瘤细胞U266对硼替佐米敏感性的相关机制研究

Mechanism Associated to Enhancing the Sensitivity of Myeloma Cells U266 to Bortezomib by 2-Methoxyestradiol
下载PDF
导出
摘要 本研究旨在探索2-甲氧基雌二醇(2-ME2)联合硼替佐米对人骨髓瘤细胞株U266的协同抑制增殖和诱导凋亡作用及其可能机制。2-ME2、硼替佐米单用以及二者联合分别处理U266细胞,用CCK8方法检测细胞增殖活力,caspase3/7活性法检测细胞凋亡,流式细胞术分析细胞周期的变化,荧光实时定量PCR检测P21、BAX、BCL-2等mRNA水平变化。结果表明:相比于2-ME2和硼替佐米单用,2-ME2联合硼替佐米处理U266细胞后,细胞增殖明显抑制(p<0.05),细胞凋亡增加(p<0.05),细胞周期阻滞于G1-S期;在mRNA水平,P21及BAX表达上调,BCL-2表达下调。结论:2-ME2联合硼替佐米能更有效地抑制U266细胞增殖和诱导凋亡,具有协同作用,其机制可能与其诱导P21及BAX表达上调有关。 This study was aimed to explore the synergistic effect of 2-methoxyestradiol(2-ME2) and bortezomib(Bor) on the proliferative inhibition and apoptosis of U266 cell line and its possible mechanism.The cells were treated with 2-ME2,Bor alone and 2-ME2 combined with Bor,respectively.The cell viability and proliferative curve were detected by CCK8,the cell apoptosis was detected by caspase 3/7 activity test,cell cycle status was analyzed by flow cytometry,and real-time PCR was used to detect the mRNA expression of P21,BAX and BCL-2.The results showed that compared with cells treated with 2-ME2 or Bor alone,the proliferative potential of cells in combination group was significantly inhibited(p〈0.05),and apoptosis rate markedly increased(p〈0.05),cell cycle was arrested at G1-S phase,the mRNA expressive level of P21 and BAX increased,while the expression of BCL-2 decreased.It is concluded that 2-ME2 combined with Bor synergistically inhibits cell proliferation and induces apoptosis in U266 cell line.The possible mechanism may be associated with its effect of up-regulating P21 and BAX expressions.
出处 《中国实验血液学杂志》 CAS CSCD 2011年第6期1424-1428,共5页 Journal of Experimental Hematology
基金 福建省自然科学基金项目资助 编号2009J01143
关键词 2-甲氧基雌二醇 硼替佐米 骨髓瘤 U266细胞 敏感性 2-methoxyestradiol bortezomib myeloma U266 cell sensitivity
  • 相关文献

参考文献19

  • 1Adams J.The proteasome:a suitable antineoplastic target.Nat RevCancer,2004;4(5):349-360. 被引量:1
  • 2Aghajanian C,Soignet S,Dizon DS,et al.A phase I trial of thenovel proteasome inhibitor PS341 in advanced solid tumormalignancies.Clin Cancer Res,2002;8(8):2505-2511. 被引量:1
  • 3Richardson PG,Sonneveld P,Schuster MW,et al.Bortezomib orhigh-dose dexamethasone for relapsed multiple myeloma.N Engl JMed,2005;352(24):2487-2498. 被引量:1
  • 4Kumar S,Rajkumar SV.Many facets of bortezomib resistance/susceptibility.Blood,2008;112(6):2177-2178. 被引量:1
  • 5Lakhani NJ,Sarkar MA,Venitz J,et al.2-Methoxyestradiol,apromising anticancer agent.Pharmacotherapy,2003;23(2):165-172. 被引量:1
  • 6Mooberry SL.New insights into 2-methoxyestradiol,a promisingantiangiogenic and antitumor agent.Curr Opin Oncol,2003;15(6):425-430. 被引量:1
  • 7Kumar AP,Garcia GE,Orsborn J,et al.2-Methoxyestradiolinterferes with NF kappa B transcriptional activity in primitiveneuroectodermal brain tumors:implications for management.Carcinogenesis,2003;24(2):209-216. 被引量:1
  • 8Florczak U,Toulany M,Kehlbach R,et al.2-Methoxyestradiol-induced radiosensitization is independent of SOD but depends oninhibition of Akt and DNA-PKcs activities.Radiother Oncol,2009;92(3):334-338. 被引量:1
  • 9Zou H,Zhao S,Zhang J,et al.Enhanced radiation-inducedcytotoxic effect by 2-ME in glioma cells is mediated by induction ofcell cycle arrest and DNA damage via activation of ATM pathways.Brain Res,2007;1185:231-238. 被引量:1
  • 10Hideshima T,Mitsiades C,Akiyama M,et al.Molecularmechanisms mediating antimyeloma activity of proteasome inhibitorPS-341.Blood,2003;101(4):1530-1534. 被引量: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