Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells.
Antitumor effect of cetuximab in combination with S-1 in EGFR-amplified gastric cancer cells.
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DOI：
10.3892/ijo.2011.1279
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发表时间：
2012-04
影响因子：
5.2
通讯作者：
Kitagawa Y
中科院分区：
文献类型：
--
作者：
Fukuda K;Saikawa Y;Takahashi M;Takahashi T;Wada N;Kawakubo H;Takeuchi H;Kitagawa Y
人表皮生长因子受体（EGFR）的过度表达已在胃癌（GC）中检测到，并与不良结局相关。EGFR靶向药物和细胞毒性药物的联合治疗方案被认为是EGFR过表达GC的潜在治疗选择。在此，我们研究了口服氟尿嘧啶S-1和EGFR靶向药物西妥昔单抗联合治疗在有或无EGFR过表达的GC细胞中的作用。通过流式细胞术和定量PCR测定GC细胞中EGFR的表达。使用实验性5-氟尿嘧啶（5 FU）代替S-1进行体外实验。在体外和体内检查了5 FU或西妥昔单抗单药治疗或5 FU/西妥昔单抗联合治疗的疗效。通过免疫组织化学（IHC）检查临床标本的EGFR。EGFR表达评分定义为至少50-75%的细胞膜和细胞质染色较强。5 FU和西妥昔单抗的组合协同抑制细胞增殖，并在EGFR过表达的GC细胞中表现出增强的促凋亡作用。西妥昔单抗还诱导EGFR和AKT磷酸化的下调，导致信号传导减弱。S-1和西妥昔单抗联合给药的体内抗肿瘤作用也大于任何一种药物单独给药。因此，我们的临床前研究结果表明，S-1和EGFR靶向治疗的组合是一个有前途的治疗选择胃癌与EGFR过表达。
Overexpression of human epidermal growth factor receptor (EGFR) has been detected in gastric cancer (GC) and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting agents and cytotoxic agents are considered to be a potential therapeutic option for EGFR-overexpressing GC. Herein, we have investigated the effects of combination treatment with the oral fluoropyrimidine S-1 and the EGFR-targeting agent cetuximab in GC cells with or without EGFR overexpression. EGFR expression was determined by FACS and quantitative PCR in GC cells. Experimental 5-fluorouracil (5FU) was used instead of S-1 for in vitro experiments. The efficacy of 5FU or cetuximab monotherapy or combination 5FU/cetuximab therapy was examined in vitro and in vivo. Clinical specimens were examined for EGFR by immunohistochemistry (IHC). EGFR expression score was defined as strong membrane and cytoplasmic staining in at least 50–75% of cells. The combination of 5FU and cetuximab synergistically inhibited cell proliferation and exhibited an enhanced proapoptotic effect in GC cells with EGFR overexpression. Cetuximab also induced down-regulation of phosphorylation of EGFR and AKT, leading to diminished signaling. The antitumor effect of the combination of S-1 and cetuximab in vivo was also greater than that of either drug alone. Our preclinical findings thus indicate that the combination of S-1 and EGFR-targeting therapy is a promising treatment option for GC with EGFR overexpression.
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DOI：
10.1016/s0140-6736(09)60617-6
发表时间：
2009-08-08
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hartgrink HH;Jansen EP;van Grieken NC;van de Velde CJ
通讯作者：
van de Velde CJ
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK
影响因子：
45.3
作者：
Hanna, Nasser;Lilenbaum, Rogerio;Bonomi, Philip
通讯作者：
Bonomi, Philip
影响因子：
158.5
作者：
Cunningham, D;Humblet, Y;Van Cutsem, E
通讯作者：
Van Cutsem, E
影响因子：
158.5
作者：
Sakuramoto, Shinichi;Sasako, Mitsuru;Arai, Kuniyoshi
通讯作者：
Arai, Kuniyoshi