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丙戊酸协同伊马替尼诱导K562细胞凋亡并下调Bcr/AblmRNA和磷酸化蛋白激酶B的表达

Valproate enhances imatinib-induced apoptosis and down-regulates Bcr/Abl mRNA and phosphorylated protein kinase B in chronic myeloid leukemia cell line K562
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摘要 目的:探讨丙戊酸联合伊马替尼对慢性粒细胞白血病细胞株K562凋亡的影响,同时探索其可能的作用机制。方法:K562细胞分别用丙戊酸、伊马替尼以及两药联合处理。检测各组细胞在药物处理后的细胞周期、细胞凋亡、Bcr/Abl mRNA水平、总蛋白激酶B(PKB)以及磷酸化PKB(p-PKB)水平。结果:丙戊酸组、伊马替尼组和两药联用组K562细胞凋亡率分别为(11.47±0.25)%、(28.43±1.70)%和(57.73±4.38)%(P<0.05),对于细胞周期各指标,两药联用组与单药组无明显差异。Bcr/Abl mRNA以及p-PKB在丙戊酸组、伊马替尼组和两药联用组的水平分别为(0.00±0.00)、(64.17±12.27)和(0.00±0.00)×109copies/(g total mRNA)以及0.25±0.02、0.17±0.01和0.08±0.01(均P<0.05),总PKB 3组细胞间无明显差异。结论:丙戊酸能协同伊马替尼促进K562细胞凋亡,其作用机制可能与降低Bcr/Abl mRNA和p-PKB水平有关。 AIM: To investigate the effects of valproate and imatinib on the apoptosis of chronic myeloid leuke- mic cell line K562. METHODS: K562 cells were divided into 3 groups and treated with valproate, imatinib and cotreat- ment, respectively. Cell cycle, apeptosis, the mRNA expression of Bcr/Abl, total protein kinase B (PKB) and phospho- rylated PKB (p-PKB) were analyzed. RESULTS: The apoptotic rates in valproate group, imatinib group and cotreatment group were ( 11.47 ±0.25 ) %, (28.43 ±1.70) % and (57.73± 4.38) %, respectively (P 〈 0.05 ). No obvious differ- ence was observed in cell cycle between cotreatment group and monodrug group. Bcr/Abl mRNA and p-PKB in the above 3 groups were (0.00 ± 0.00), (64.17 ± 12.27), and ( 0.00 ± 0.00 ) x 109 copies/( g total mRNA), respectively ( P 〈 0. 05), and 0.25 ±0.02, 0.17 ± 0.01 and 0.08 ± 0.01, respectively ( P 〈 0.05 ). No apparent difference of PKB was found in the 3 groups. CONCLUSION: Valproate enhances imatinib-induced apoptosis and may link to the down-regula- tion of Bcr/Abl mRNA and p-PKB in chronic myeloid leukemic cell line K562.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2014年第1期61-66,共6页 Chinese Journal of Pathophysiology
基金 广东省自然科学基金资助项目(No.06021340) 广东省科技厅社会发展项目(No.2009B030803033)
关键词 丙戊酸 白血病 髓样 慢性 细胞凋亡 融合蛋白 BCR ABL 蛋白激酶B Valproic acid Leukemia, myeloid, chronic Apoptosis Fusion proteins, Bcr/Abl Protein kinase B
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参考文献16

  • 1Li XN, Shu Q, Su JM, et al. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expres- sion of p21Cip1 ,CDK4,and CMYC[J]. Mol Cancer Ther, 2005,4(12) : 1912-1922.
  • 2Bastian L, Hof J, Pfau M, et al. Synergistic activity of bortezomib and HDACi in preclinical models of B-cell pre- cursor acute lymphoblastic leukemia via modulation of p53, PI3K/AKT, and NF-κB[J]. Clin Cancer Res,2013, 19(6) :1445-1457.
  • 3张祥忠,尹爱华,许多荣,朱小玉,何敏,丁倩,李娟,陈运贤.丙戊酸钠对慢性粒细胞白血病细胞株K562增殖和凋亡的影响[J].中山大学学报(医学科学版),2008,29(5):562-565. 被引量:1
  • 4Kostrouchova. M, Kostrouch Z, Kostrouchova M, Valproic acid, a molecular lead to multiple regulatory pathways [J]. Folia Biol (Praha), 2007,53(2) :37-49.
  • 5张祥忠,尹爱华,刘建华,朱小玉,何敏,丁倩,陈运贤.丙戊酸钠诱导K562细胞周期阻滞和凋亡并上调p^21WAF1基因mRNA的表达[J].中国病理生理杂志,2008,24(9):1726-1729. 被引量:6
  • 6Zhang XZ, Yin AH ; Zhu XY, et al. Using an exon mi- croarray to identify a global profile of gene expression and alternative splicingin K562 cells exposed to sodium val- proate[J]. Oncol Rep,2012,27(4) : 1258-1265.
  • 7Zhang XZ, Yin AH, Lin D J, et al. Analyzing gene expres- sion profile in K562 cells exposed to sodium valproate u- sing microarray combined with the connectivity map data- base[ J]. J Biomed Biotechnol, 2012,2012:654291.
  • 8Buchi F, Pastorelli R, Ferrari G, et al. Acetylome and phosphoproteome modifications in imatinib resistant chron- ic myeloid leukaemia cells treated with valproic acid [ J ]. Leuk Res,2011,35(7) :921-931.
  • 9Morotti A, Cilloni D, Messa F, et al. Valproate enhances imatinib-induced growth arrest and apoptosis in chronic myeloid leukemia cells [ J ]. Cancer, 2006,106 ( 5 ) : 1188- 1106.
  • 10Yu C, Rahmani M, Almenara J, et al. Histone deacety- lase inhibitors promote STI571-mediated apoptosis in STI571-sensitive and -resistant Bcr/Abl^+ human myeloid leukemia cells [ J ]. Cancer Res, 2003, 63 (9) : 2118- 2126.

二级参考文献23

  • 1王重韧,黄强.脂肪酸类药物诱导分化治疗脑胶质瘤分子机制研究[J].中华神经医学杂志,2005,4(2):197-200. 被引量:3
  • 2薛红漫,李文益,郭海霞,夏焱,陈琴,刘勇.丙戊酸诱导白血病细胞凋亡机理的实验研究[J].中华儿科杂志,2005,43(12):894-898. 被引量:12
  • 3李新刚,陈燕,吴青,孙春艳.姜黄素对人淋巴瘤Raji细胞组蛋白H3乙酰化作用的影响[J].癌症,2006,25(5):582-586. 被引量:8
  • 4Takai N, Desmond JC, Kumagai T, et al. Histone deacetylase inhibitors have a profound antigrowth activity in endometrial cancer cells [J]. Clin Cancer Res, 2004,10(3):1141-1149.
  • 5Li XN, Shu Q, Su JM, et al. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating expression of p21Cip1, CDK4, and CMYC [J]. Mol Cancer Ther, 2005,4(12) : 1912-1922.
  • 6Gurvich N, Tsygankova OM, Meinkoth JL, et al. Histone deacetylase is a target of valproic acid-mediated cellular differentiation [ J ]. Cancer Res, 2004,64 ( 3 ) : 1079-1086.
  • 7Tony H. Treatment for chronic myelogenous leukemia: the long road to imatinib[J]. J Clin Invest, 2007,117 (8) : 2036-2043.
  • 8Minucci S, Nervi C, Lo Coco F, et al. Histone deacetylases : a common molecular target for differentiation treatment of acute myeloid leukemias? [J]. Oncogene, 2001, 20(24) : 3110-3115.
  • 9Weidle U H, Grossmann A. Inhibition of histone deacetylases: a new strategy to target epigenetic modifications for anticancer treatment [J]. Anticancer Res, 2000, 20(3A) : 1471-1485.
  • 10Tang R, Faussat A M, Majdak P, et al. Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1 [J]. Leukemia, 2004,18(7) : 1246-1251.

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