Mechanism by which interferon reduces the resistance of MGMT positive glioma stem cells to temozolomide

doi:10.3969/j.issn.2095-4344.2015.36.011

Abstract

Abstract:

BACKGROUND: It is easy to appear the phenomenon of drug resistance in the treatment of patients with glioma, and O(6)-methylguanine-DNA methyltransferase (MGMT) is a kind of multidrug resistance gene expressed in glioma.

OBJECTIVE: To investigate the role of interferon to increase the sensibilization of MGMT positive glioma stem cells to temozolomide in vitro.

METHODS: Glioma cell lines, U251 and SKMG-4, were induced by suspended cloning ball formation method to harvest MGMT positive glioma stem cells, U251G and SKMG-4G. Cell counting kit-8 assay was used to detect the killing effect of interferon α/β combined with temozolomide on MGMT positive glioma stem cells. RT-PCR and western blot assay were employed to determine the expression of MGMT and nuclear factor κB in MGMT positive glioma stem cells.

RESULTS AND CONCLUSION: Western blot results showed positive expression of MGMT in U251G and SKMG-4G cells at protein levels. After intervention with interferon α/β, the mRNA expression of MGMT and nuclear factor κB in SKMG-4G and U251G cells was reduced significantly, and then further decreased after temozolomide treatment. These findings indicate that interferon α/β can remarkably strengthen the killing effect of temozolomide on MGMT positive glioma stem cells.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Glioma, Neoplastic Stem Cells, Interferons, O(6)-Methylguanine-DNA Methyltransferase

CLC Number:

R394.2

Su Hui, Liu Zhao-wei, Du Hong-li, Qiao Yan-mei. Mechanism by which interferon reduces the resistance of MGMT positive glioma stem cells to temozolomide[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(36): 5800-5805.

Figures/Tables 2

References

[1] 郭颖,曲彦明,韩松,等.血管细胞黏附分子-1蛋白在人脑胶质瘤组织内表达改变及其临床意义[J].基础医学与临床,2013,33(12): 1600-1604.

[2] 曾宪起,申长虹,浦佩玉,等.应用替莫唑胺对照司莫司丁治疗恶性脑胶质瘤的疗效观察[J].中华神经外科杂志,2006,22(4): 204-207.

[3] 黄磊,江涛,袁芳,等.胶质瘤染色体1p和19q杂合性缺失与O6-甲基鸟嘌呤DNA甲基转移酶p53和Ki-67蛋白表达的关系[J].中华肿瘤杂志,2011,33(10):752-758.

[4] 高彩凤,刘庆荣,刘洪涛.雷利度胺联合干扰素对多发性骨髓瘤U266细胞肿瘤坏死因子相关凋亡诱导配体及其受体表达的影响[J].中国慢性病预防与控制,2015,23(1):52-53.

[5] Groves MD, Puduvalli VK, Gilbert MR, et al. Two phase II trials of temozolomide with interferon-alpha2b (pegylated and non-pegylated) in patients with recurrent glioblastoma multiforme. Br J Cancer. 2009;101(4):615-620.

[6] 刘晓晗.SOX2在脑胶质瘤组织中的表达及其与临床病理特征的关系[J].山东医药,2014,54(30):40-42.

[7] 李响,韩圣,秦晓飞,等.不同级别胶质瘤中P53蛋白与O6-甲基鸟嘌呤-DNA甲基转移酶表达的区别与联系[J].中国医科大学学报, 2014,43(6):499-501,522.

[8] 张杏兰,张杏红.尼妥珠单抗联合放化疗治疗脑胶质母细胞瘤的观察和护理[J].医学信息,2012,25(3):230-231.

[9] 权俊杰,周乐,付海燕,等.替莫唑胺化疗联合放疗对弥漫性内生型脑干胶质瘤临床疗效及预后分析[J].临床和实验医学杂志, 2015, 14(4):310-313.

[10] 黄从刚,郭振涛,陈谦学,等.胶质瘤U251耐替莫唑胺细胞株放射照射后细胞周期及P-糖蛋白表达变化[J].中华实验外科杂志, 2014, 31(9):1883-1885.

[11] 权俊杰,周乐,付海燕,等.替莫唑胺化疗联合放疗对弥漫性内生型脑干胶质瘤临床疗效及预后分析[J].临床和实验医学杂志,2015, 14(4):310-313.

[12] 彭东崑,彭雁,桑卉.顺铂联合替莫唑胺治疗复发性恶性脑胶质瘤的近期疗效观察[J].中国医药指南,2015,13(10):105-106.

[13] 黄仁华,侯艳丽,徐欣,等.脑胶质瘤术后三维适形放疗联合替莫唑胺疗效分析[J].肿瘤学杂志,2015,21(3):219-222.

[14] 陈婵娟,王家祺,梁永,等.替莫唑胺联合贝伐单抗同步放疗对高级别脑胶质瘤术后患者的疗效分析[J].肿瘤药学,2015,5(2): 26-129.

[15] 于喜贞,韩光魁,杨文涛,等.替莫唑胺对神经胶质瘤TJ905细胞增殖特性和迁移能力的影响[J].新乡医学院学报,2015,32(2): 111-114.

[16] 颜元良,钱龙,龚志成.国内调强放疗联合替莫唑胺化疗治疗恶性脑胶质瘤疗效的Meta分析[J].中国临床药理学与治疗学,2015, 20(1):64-69.

[17] 杨丽萍,侯俊德,段爱红,等.肿瘤干细胞标志物CD133和Ki67在卵巢癌中的表达及意义[J].临床和实验医学杂志,2015,14(5): 368-370.

[18] 张庆,赵文超,韩娜.肿瘤干细胞在人宫颈癌细胞株SiHa耐顺铂效应中的作用[J].中国妇幼保健,2015,30(12):1908-1911.

[19] 杨丽萍,侯俊德,段爱红,等.肿瘤干细胞标志物CD133和Nestin在卵巢癌中的表达及意义[J].临床和实验医学杂志,2015,14(4): 301-304.

[20] 蔡文品,林德照,黄友泽,等.CD133在直肠癌组织中的表达及与临床病理参数的相关性[J].中国卫生检验杂志,2015,25(4): 529-531.

[21] 于杰,崔晓旭,孙雯雯.悬浮培养法富集结肠癌肿瘤干细胞的研究[J].中国慢性病预防与控制,2015,23(4):271-274.

[22] 曾海娥.肿瘤干细胞在肿瘤治疗中的应用探讨[J].中国医药指南, 2015,13(4):189-190.

[23] Wang JD, He B, Dai WB, et al. Targeting glioblastoma cancer stem cell marker CD133 by heptapeptide-modified DSPE-PEG micelles. Journal of Chinese Pharmaceutical Sciences. 2015;24(1):34-39.

[24] 李姗姗,王丽,边育红.基于肿瘤干细胞的恶性肿瘤靶向治疗策略[J].中国细胞生物学学报,2015,37(2):309-314.

[25] 李文鹏,罗维远,徐毅,等.下调Oct4基因表达对MDA-MB-231乳腺癌干细胞生物学特性的影响[J].中华肿瘤杂志,2015,37(4): 251-257.

[26] 杨阳,林盛,黄佳妮,等. CD133+卵巢癌干细胞通过CXCL16/ CXCR6维持其侵袭迁移能力J].第三军医大学学报,2015,37(8): 757-761.

[27] 吴红茜,张秀娜,高晓芳,等.干扰素调节因子8与肿瘤的关系研究[J].安徽医药,2014,18(9):1609-1613.

[28] 邱晓昕,刘景诗,左朝晖.α-干扰素和环氧合酶-2抑制剂对人肝癌细胞生长的抑制作用[J].中华实验外科杂志,2014,31(9):1932.

[29] 于甜,胡小鹏,祝小红,等.干扰素及肿瘤坏死因子抗病毒作用研究进展[J].中国免疫学杂志,2014,30(3):409-415.

[30] 熊辉,付丽萍,周琳.干扰素对肿瘤的抑制作用[J].华中科技大学学报:医学版,2014,43(5):599-602.

[31] Colman H, Berkey BA, Maor MH, et al. Phase II Radiation Therapy Oncology Group trial of conventional radiation therapy followed by treatment with recombinant interferon-beta for supratentorial glioblastoma: results of RTOG 9710. Int J Radiat Oncol Biol Phys. 2006;66(3): 818-824.

[32] 任春霞,徐娜,宋亚琴,等.癌相关成纤维细胞通过Gro-α激活NF-кB核转位和VEGF表达促进卵巢癌的生长[J].中国癌症杂志,2014,24(5):321-328.

[33] 王文举,李鸿钧,孙茂盛,等.NF-κB与持久炎症及肿瘤发生关系[J].生命的化学,2007,27(3):197-199.

[34] 杜正云,肖宝荣,翟西菊,等.核因子-κB与肿瘤放射治疗[J].国际肿瘤学杂志,2014,41(7):503-507.

[35] 邢飞跃,赵克森,姜勇,等.NF-κB的信号通路与阻断策略[J].中国病理生理杂志,2003,19(6):849-855.

[36] 崔嵩,刘学锋,吴斌.NF-κB在肿瘤中的研究进展[J].现代肿瘤医学,2009,17(1):134-137.

[37] 沈冬,仇志坤,陈银生,等.干扰素-α/β体外增敏替莫唑胺对MGMT阳性胶质瘤干细胞作用[J].中山大学学报:医学科学版,2012, 33(3):368-372

[38] 张建国,李玉,刘正国,等.少突胶质细胞肿瘤1p/19q联合缺失与p53、10号染色体上磷酸酶及张力蛋白同源物和6-甲基鸟嘌呤-DNA甲基转移酶蛋白表达的关系[J].中华实验外科杂志,2012, 29(8):1559-1562.