Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status.
Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status.
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DOI：
10.1038/sj.bjc.6604222
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发表时间：
2008-02-26
影响因子：
8.8
通讯作者：
Nakagawa, K.
中科院分区：
文献类型：
--
作者：
Akashi, Y.;Okamoto, I.;Iwasa, T.;Yoshida, T.;Suzuki, M.;Hatashita, E.;Yamada, Y.;Satoh, T.;Fukuoka, M.;Ono, K.;Nakagawa, K.
关键词：
表皮生长因子受体（EGFR）的表达和活性是几种肿瘤类型（包括非小细胞肺癌（NSCLC））放射敏感性的决定因素。然而，关于NSCLC细胞中EGFR的遗传改变是否影响EGFR单克隆抗体（mAb）联合放射治疗的治疗反应，目前知之甚少。我们研究了尼妥珠单抗（EGFR的人源化mAb）联合电离辐射对不同EGFR状态的人NSCLC细胞系的影响。流式细胞术显示H292和Ma-1细胞分别在细胞表面表达高水平和中等水平的EGFR，而H460、H1299和H1975细胞显示低水平的表面EGFR表达。免疫印迹分析显示，EGFR磷酸化抑制尼妥珠单抗在H292和Ma-1细胞，但不是在H460，H1299，或H1975细胞。在体外克隆形成试验中，尼妥珠单抗增强了H292和Ma-1细胞中放射的细胞毒性作用，剂量增强因子分别为1.5和1.3。它还增强了辐射对H292和Ma-1细胞裸鼠移植瘤的抗肿瘤作用，增强因子分别为1.3和4.0。尼妥珠单抗在体外和体内均不影响H460细胞的放射反应。尼妥珠单抗在体外和体内增强了某些人NSCLC细胞系中放射的抗肿瘤疗效。这种效应可能与细胞表面EGFR表达水平有关，而不是EGFR突变。
The expression and activity of the epidermal growth factor receptor (EGFR) are determinants of radiosensitivity in several tumour types, including non-small cell lung cancer (NSCLC). However, little is known of whether genetic alterations of EGFR in NSCLC cells affect the therapeutic response to monoclonal antibodies (mAbs) to EGFR in combination with radiation. We examined the effects of nimotuzumab, a humanised mAb to EGFR, in combination with ionising radiation on human NSCLC cell lines of differing EGFR status. Flow cytometry revealed that H292 and Ma-1 cells expressed high and moderate levels of EGFR on the cell surface, respectively, whereas H460, H1299, and H1975 cells showed a low level of surface EGFR expression. Immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in H292 and Ma-1 cells but not in H460, H1299, or H1975 cells. Nimotuzumab augmented the cytotoxic effect of radiation in H292 and Ma-1 cells in a clonogenic assay in vitro, with a dose enhancement factor of 1.5 and 1.3, respectively. It also enhanced the antitumor effect of radiation on H292 and Ma-1 cell xenografts in nude mice, with an enhancement factor of 1.3 and 4.0, respectively. Nimotuzumab did not affect the radioresponse of H460 cells in vitro or in vivo. Nimotuzumab enhanced the antitumor efficacy of radiation in certain human NSCLC cell lines in vitro and in vivo. This effect may be related to the level of EGFR expression on the cell surface rather than to EGFR mutation.
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DOI：
10.1016/j.ijrobp.2004.01.053
发表时间：
2004-01-01
影响因子：
7
作者：
Bonner, JA;Buchsbaum, DJ;Raisch, KP
通讯作者：
Raisch, KP
影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
11.2
作者：
Das, Amit K.;Sato, Mitsuo;Nirodi, Chaitanya S.
通讯作者：
Nirodi, Chaitanya S.
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B
DOI：
10.1016/s0360-3016(03)00511-x
发表时间：
2003-09-01
影响因子：
7
作者：
Liang, K;Ang, KK;Fan, Z
通讯作者：
Fan, Z