Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer.
Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer.
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DOI：
10.1038/bjc.2012.321
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发表时间：
2012-08-07
影响因子：
8.8
通讯作者：
Oya, M.
中科院分区：
文献类型：
--
作者：
Kozakai, N.;Kikuchi, E.;Hasegawa, M.;Suzuki, E.;Ide, H.;Miyajima, A.;Horiguchi, Y.;Nakashima, J.;Umezawa, K.;Shigematsu, N.;Oya, M.
诱导活化核因子(NF)-κB是抵抗放射治疗的前列腺癌细胞的主要机制之一。我们假设用一种新的NF-κB抑制剂DHMEQ使可诱导的NF-κB失活，可以提高放疗的治疗效果。PC-3和LNCaP细胞分别暴露于辐照和/或DHMEQ。细胞活力、细胞周期分析、western blot检测及NF-κB活性测定。并对辐照联合DHMEQ在体内的抗肿瘤作用进行了评价。与单独照射相比，DHMEQ联合照射可抑制细胞生长和G2/M阻滞。DHMEQ处理可抑制辐照诱导的NF-κB活性。LNCaP中p53、p21的表达和PC-3细胞中14-3-3σ的表达均增加。在体内研究中，治疗开始后64天，联合治疗组的肿瘤大小分别比未治疗对照组、单独治疗组和单独照射组小85.1%、77.1%和64.7%。用DHMEQ阻断辐射诱导的NF-κB活性，可克服放射耐药反应，有望成为治疗前列腺癌的新治疗方式。
Inducible activation of nuclear factor (NF)-κB is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-κB with a novel NF-κB inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy. PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-κB activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed. The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-κB activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3σ in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively. Blockade of NF-κB activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.
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染料木黄酮抑制辐射诱导的NF-kappab在促进凋亡和G2/M细胞周期停滞的前列腺癌细胞中的激活。
影响因子：
3.8
作者：
Raffoul, Julian J.;Wang, Yu;Kucuk, Omer;Forman, Jeffrey D.;Sarkar, Fazlul H.;Hillman, Gilda G.
通讯作者：
Hillman, Gilda G.
影响因子：
11.5
作者：
Kuroda, K;Horiguchi, Y;Murai, M
通讯作者：
Murai, M
影响因子：
64.8
作者：
Tang, GL;Minemoto, Y;Lin, A
通讯作者：
Lin, A
影响因子：
7.5
作者：
Takatsuna, H;Umezawa, K
通讯作者：
Umezawa, K
影响因子：
8
作者：
Palayoor, ST;Youmell, MY;Price, BD
通讯作者：
Price, BD